Refine
Is part of the Bibliography
- yes (399)
Year of publication
Document Type
- Journal article (221)
- Doctoral Thesis (156)
- Book article / Book chapter (14)
- Conference Proceeding (6)
- Review (2)
Keywords
- Toxikologie (121)
- DNA damage (18)
- Oxidativer Stress (16)
- micronuclei (13)
- oxidative stress (13)
- Adenosinrezeptor (12)
- DNS-Schädigung (12)
- genotoxicity (12)
- Fluoreszenz-Resonanz-Energie-Transfer (10)
- GPCR (10)
- Mikrokerne (10)
- Adenosine receptors (9)
- G-Protein gekoppelte Rezeptoren (9)
- Angiotensin II (7)
- Biomarker (7)
- FRET (7)
- Genotoxizität (7)
- Herzinsuffizienz (7)
- DNA (6)
- Genotoxicity (6)
- Gentoxizität (6)
- Maus (6)
- Mutagenität (6)
- Pharmakologie (6)
- cAMP (6)
- genomic damage (6)
- heart failure (6)
- Adenosin (5)
- Aldosteron (5)
- Carcinogen (5)
- DNA binding (5)
- Dimerisierung (5)
- ERK1/2 (5)
- G-protein (5)
- Kleinkern (5)
- MAP-Kinase (5)
- Medizin (5)
- Micronuclei (5)
- Toxizität (5)
- biomarker (5)
- nephrotoxicity (5)
- Adenylate cyclase (4)
- Calcium (4)
- Comet Assay (4)
- Cyclo-AMP (4)
- DNA-Schaden (4)
- G proteins (4)
- Genomschaden (4)
- Herzhypertrophie (4)
- Inhibition (4)
- Niere (4)
- apoptosis (4)
- bariatric surgery (4)
- calcium (4)
- cardiac hypertrophy (4)
- comet assay (4)
- metabolism (4)
- micronucleus test (4)
- mutagenicity (4)
- mycotoxin (4)
- signal transduction (4)
- toxicity (4)
- 1 (3)
- Adrenerger Rezeptor (3)
- Beta-Rezeptor (3)
- Biotransformation (3)
- Carcinogenesis (3)
- Carcinogenicity (3)
- Carcinogens (3)
- Chronophin (3)
- Dialyse (3)
- Enzyme induction (3)
- Ernährung (3)
- G protein-coupled receptors (3)
- G-Protein (3)
- Hormone (3)
- Hypertonie (3)
- In vitro (3)
- Insulin (3)
- LC-MS (3)
- Leber (3)
- Magenchirurgie (3)
- Metabolismus (3)
- Mikrokern (3)
- Mikrokerntest (3)
- Muscarinrezeptor (3)
- NADPH-Oxidase (3)
- Nephrotoxizität (3)
- Nichtionisierende Strahlung (3)
- PDXP (3)
- Phosphatase (3)
- Phosphatasen (3)
- Phosphoglykolatphosphatase (3)
- Pneumolysin (3)
- Pyridoxalphosphat (3)
- RKIP (3)
- Rezeptor (3)
- Signaltransduktion (3)
- Zelle (3)
- cancer (3)
- carcinogenicity (3)
- cytoskeleton (3)
- differentiation (3)
- fluorescence resonance energy transfer (3)
- heart (3)
- hypertension (3)
- inflammation (3)
- liver (3)
- transcription factors (3)
- 18F-FDG (2)
- 5-Azacytidine (2)
- A1 adenosine receptors (2)
- Actin (2)
- Adenosine receptor (2)
- Adipositas (2)
- Aflatoxin (2)
- Alpha-2-Rezeptor (2)
- Ames test (2)
- Anthocyane (2)
- Apoptose (2)
- Apoptosis (2)
- Autoimmunerkrankung (2)
- BRET (2)
- Bakteriengift (2)
- Benfotiamin (2)
- Benzene (2)
- Bestrahlung (2)
- Beta-1-Rezeptor (2)
- Brustkrebs (2)
- Carcinogenese (2)
- Carcinogenität (2)
- DNA Binding (2)
- DNA Schaden (2)
- DNA repair (2)
- DNS-Schaden (2)
- DNS-Strangbruch (2)
- Diethylstilbestrol (2)
- Dose response (2)
- Dose-response relationship (2)
- Dosis-Wirkungs-Beziehung (2)
- Electropermeabilization (2)
- Elektrofusion (2)
- Elektroporation (2)
- Estrogen (2)
- FCS (2)
- Fluoreszenz (2)
- Furan (2)
- Förster Resonanz Energie Transfer (2)
- G protein coupled receptor (2)
- G-Protein gekoppelter Rezeptor (2)
- G-protein coupled receptor (2)
- Genetic instability (2)
- HPLC-MS (2)
- Heart failure (2)
- Herz (2)
- Hirnhautentzündung (2)
- Huh6 (2)
- Hypertrophie (2)
- Hämatopoetische Stammzellen (2)
- Hämodialyse (2)
- Inhalation (2)
- Kanzerogenese (2)
- Kardiomyopathie (2)
- Kongestive Herzmuskelkrankheit (2)
- Krebs (2)
- L5178Y cells (2)
- Lasiocarpin (2)
- Meningitis (2)
- Merkaptursäuren (2)
- Metabonomics (2)
- Micronucleus (2)
- Mikroskopie (2)
- Myokarditis (2)
- N-formyl peptides (2)
- Noradrenalin (2)
- PDE (2)
- PET (2)
- Paracetamol (2)
- Parathormon (2)
- Peptidtherapie (2)
- Pharmakokinetik (2)
- Pharmazie (2)
- Phosducin (2)
- Phosphodiesterase (2)
- Pyrrolizidinalkaloide (2)
- QIVIVE (2)
- Radioligand binding (2)
- Raf kinase inhibitor protein (2)
- Raf-Kinasen (2)
- Rat (2)
- Regulation (2)
- Reproductive toxicity (2)
- Risikoanalyse (2)
- Risk Assessment (2)
- Salmonella/microsome assay (2)
- Silicones (2)
- Sulforaphan (2)
- Terahertzbereich (2)
- Terahertzstrahlung (2)
- Toxicology (2)
- Toxin (2)
- Transgene Tiere (2)
- Zellkultur (2)
- Zellzyklus (2)
- actin (2)
- actinomycetes (2)
- adenosine (2)
- adenosine receptor (2)
- adenosine receptors (2)
- aldosterone (2)
- barbiturates (2)
- bariatrische Chirurgie (2)
- beta-adrenerge Signalwege (2)
- biased signaling (2)
- binding (2)
- biomedicine, general (2)
- cGMP (2)
- cancer risk (2)
- carcinogen (2)
- cell culture (2)
- cisplatin (2)
- classification (2)
- comet-assay (2)
- cytokinins (2)
- dialysis (2)
- dialysis patients (2)
- environmental health (2)
- estrogen (2)
- familial DCM (2)
- fluorescence (2)
- furan (2)
- immunohistochemistry (2)
- in-vivo (2)
- insulin (2)
- kidney (2)
- kidneys (2)
- lymphocytes (2)
- mast cells (2)
- medicine (2)
- membrane skeleton (2)
- meningitis (2)
- mercapturic acid (2)
- mercapturic acids (2)
- metabonomics (2)
- myocarditis (2)
- non-ionizing radiation (2)
- obesity (2)
- occupational medicine/industrial medicine (2)
- oxidativer Stress (2)
- peripheral lymphocytes (2)
- pharmacogenetics (2)
- pharmacokinetics (2)
- pharmacology/toxicology (2)
- pneumolysin (2)
- positron emission tomography (2)
- radiation (2)
- rat brain membranes (2)
- receptors (2)
- resveratrol (2)
- risk assessment (2)
- terahertz radiation (2)
- therapy (2)
- transgen (2)
- uremic toxins (2)
- yam (2)
- Östrogene (2)
- (Mouse L-cell) (1)
- (Rat brain membrane) (1)
- (Rat liver) (1)
- (Salmonella) (1)
- 1H-NMR-Spectroscopy (1)
- 2 (1)
- 2',7'-dichlorofluorescin (1)
- 2-Acetylaminofluorene (1)
- 2-Dichloroethane (1)
- 2-Dioxetane (1)
- 2-Generation reproduction (1)
- 2-acetylaminofluorene (1)
- 3 (1)
- 3-pentafluoropropene (1)
- 3-tetrafluoropropene (1)
- 3R (1)
- 4'-hydroxylation (1)
- 4-(p-nitrobenzyl)pyridine (1)
- 4-Aminobiphenyl (1)
- 4-aminobiphenyl (1)
- 4-dial (1)
- 6-benzylaminopurine (1)
- 7,8-Dihydroxyflavon (1)
- 7,8-dihydroxyflavone (1)
- 8-Hydroxy-deoxyguanosine (1)
- 8-Oxo-2’-desoxyguanosin (1)
- 8-oxo-2'-deoxyguanosine (1)
- A(2B) receptors (1)
- A1 (1)
- A1 Adenosine receptors (1)
- A2B adenosine receptor (1)
- A2BAR (1)
- A<sub>2</sub> Adenosine receptor (1)
- AAF (1)
- ADHS (1)
- AMPK (1)
- API-Massenspektrometrie (1)
- AUM (1)
- A\(_{2A}\) adenosine receptor antagonist (1)
- Acetaminophen (1)
- Acetylcysteinderivate (1)
- Acrylamid (1)
- Acrylamide (1)
- Actin cytoskeleton (1)
- Activation (1)
- Addition (1)
- Adenosine (1)
- Adenosine receptor antagonists (1)
- Adenylatcyclaseassay (1)
- Adipositaschirurgie (1)
- Adrenalin (1)
- Adrenerger Neuronenblocker (1)
- Adrenergic Receptor (1)
- Adrenergic neurone blocking agent (1)
- Adrenergic receptor (1)
- Adrenergisches System (1)
- Adrenozeptor (1)
- Advanced glycosylation end products (1)
- Adverse Outcome Pathway (1)
- Adverse outcome pathway (AOP) (1)
- Aflatoxin B1 (1)
- Aktionspotenzial (1)
- Aktivierung (1)
- Aldosteronantagonist (1)
- Alkylantien (1)
- Alkylation (1)
- Allosterie (1)
- Alternans (1)
- Alterung (1)
- Alzheimers disease (1)
- Amino acid composition (1)
- Amino acids (1)
- Aminosäuren (1)
- Anabolieagent (1)
- Aneugene (1)
- Angewandte Toxikologie (1)
- Angiotensin (1)
- Angiotensin II Typ 1a-Rezeptor (1)
- Angiotensin-II-Blocker (1)
- Angst (1)
- Aniline derivatives (1)
- Animal model (1)
- Anthraquinone glycosides (1)
- Antibodies (1)
- Antikörper (1)
- Antimutagen (1)
- Antioxidans (1)
- Anxiety (1)
- Arsen (1)
- Aryl hydrocarbon rnonooxygenase (1)
- Arzneimittel (1)
- Astrozyt (1)
- Atherosclerosis (1)
- Atherosklerose (1)
- Atria (1)
- Aufmerksamkeits-Defizit-Syndrom (1)
- Autofocus (1)
- Azole (1)
- Azoles (1)
- B cells (1)
- BETA(2)-adrenergic receptor (1)
- BG-1 Zellen (1)
- BG-1 cells (1)
- BMS-5 (1)
- Background DNA damage (1)
- Bacterial Toxins (1)
- Bacterial meningitis (1)
- Bakterielle Hirnhautentzündung (1)
- Bakterien (1)
- Barbiturat (1)
- Barbiturates (1)
- Bcl-2 (1)
- Benzefuran dioxetane (1)
- Benzefuran epoxide (1)
- Benzo(a)pyrene-DNA binding (1)
- Berenil (1)
- Beta(1)-adrenergic receptor (1)
- Beta(2)-adrenergic receptor (1)
- Beta- adrenergic receptors (1)
- Beta-1-receptor (1)
- Beta-Adrenergic Receptor (1)
- Beta-Adrenozeptor (1)
- Beta-Receptor subtypes (1)
- Beta-Rezeptor Subtypen (1)
- Beta-adrenerge Rezeptoren (1)
- Bilirubin (1)
- Bindungsassay (1)
- Bioluminescence resonance energy transfer (1)
- Biomarkers (1)
- Biosensor (1)
- Biostatistik (1)
- Bisphenol A (1)
- Blutbildendes System (1)
- Blutgefäß (1)
- Blutstammzelle (1)
- Bombyx mori (1)
- BrdU (1)
- Bromodeoxyuridine labeling (1)
- C1q/TNF related protein (CTRP) (1)
- C1q/tumor necrosis factor-related proteins (1)
- CAMP production (1)
- CCT (1)
- CFC replacements (1)
- CFP (1)
- CHO-Zellen (1)
- CHO-cells (1)
- CIB1 (1)
- CMF-Therapie (1)
- CRISPR/Cas9 (1)
- CTRP (1)
- CXCR4 (1)
- CYP19 (1)
- CYP51 (1)
- CaMKII (1)
- Calcium-bindende Proteine (1)
- Calciumkanal (1)
- Cancer prevention (1)
- Carcinogen risk Individual susceptibili (1)
- Carcinogenic potency (1)
- Cardiac myocyte ; Beta-Receptor ; Muscarinic receptor ; cAMP ; G-protein ; Serum (1)
- Cardiomyocyte (1)
- Caseinkinase 2 (1)
- Caspase-1 (1)
- Caveolae (1)
- Celecoxib (1)
- Cell adhesion (1)
- Cell death and comet assay (1)
- Cell transformation (1)
- Chemical carcinogenesis (1)
- Chemokine (1)
- Chemokine receptors (1)
- Chemometrie (1)
- Chemotactic receptors (1)
- Chemotherapie (1)
- Chlorfluorkohlenstoffe (1)
- Choline deficiency (1)
- Cholinesteraseinhibitor (1)
- Chromosome aberration (1)
- Chromosome distribution (1)
- Chronic heart-failure (1)
- Chronical renal failure (1)
- Clonidin (1)
- Coffein (1)
- Cofilin (1)
- Colon cancer (1)
- Comet assay (1)
- Comet-Assay (1)
- Covalent DNA binding (1)
- Covalent binding (1)
- Covalent binding index (1)
- Covalent binding index - Diethylstilbestrol (1)
- Cyclic AMP (1)
- Cyclo-GMP (1)
- Cytochalasin-B micronucleus assay (1)
- Cytochrom P450 (1)
- Cytochrome b5 (1)
- Cytokine (1)
- Cytologie (1)
- DAMGO (1)
- DCM (1)
- DES (1)
- DIPP2a (1)
- DIPP2a-Protein (1)
- DNA Damage (1)
- DNA adduct . Repair endonuclease (1)
- DNA adducts (1)
- DNA base excision repair (1)
- DNA binching (1)
- DNA damage response (1)
- DNA metabolism (1)
- DNA methylation (1)
- DNA transfection (1)
- DNA-Addukte (1)
- DNA-Binding (1)
- DNA-Damage (1)
- DNA-Reparatur (1)
- DNA-Schäden (1)
- DNA-damage (1)
- DNS (1)
- DNS-Bindung (1)
- DNS-Doppelstrangbruch (1)
- DNS-Reparatur (1)
- Datenanalyse (1)
- Depression (1)
- Dermatologie (1)
- Di (1)
- Dialysepatienten (1)
- Dialysis (1)
- Diclofenac (1)
- Dietary process-related contaminants (1)
- Differenzierung (1)
- Differenzierungszustand (1)
- Diisononyl phthalate (1)
- Dilatative Kardiomyopathie (1)
- Dilated cardiomyopathy (1)
- Dioscorea (1)
- Diskriminanzanalyse (1)
- Dopamin-beta-Hydroxylase Promotor (1)
- Dose response relationships (1)
- Drug resistance (1)
- Dualstere Liganden (1)
- Dualsteric Ligands (1)
- EAD (1)
- EGF-Rezeptor (1)
- EGF-receptor (1)
- ERK Dimerisierungsdefizienz (1)
- ERK signaling (1)
- ERK-Kaskade (1)
- ERK-Monomer (1)
- ERK-cascade (1)
- ERK1/2 Dimerisierung (1)
- ERK1/2-Autophosphorylierung (1)
- ERK2d4 (1)
- ESDR (1)
- Ecdyson (1)
- Effekt-Modifizierung (1)
- Eierstockkrebs (1)
- Einwärtsgleichrichtung (1)
- Einzelzellgelelektrophorese (1)
- Electric Field (1)
- Electrical breakdown (1)
- Electrophiles (1)
- Elektrokardiogramm (1)
- Elektromagnetische Felder (1)
- Embryonalen Stammzellen (1)
- Embryonalentwicklung (1)
- Emodin (1)
- Empfindlichkeit (1)
- Endogenous genotoxicity (1)
- Endokrinologie (1)
- Endothelzelle (1)
- Endozytose (1)
- Entzündung (1)
- Epac (1)
- Epigenetik (1)
- Epoxide hydrolase (1)
- Erk1/2 (1)
- Ersatzstoff (1)
- Erythrozyt (1)
- Estrone (1)
- Ethionine (1)
- Eukaryotic cell (1)
- Excitotoxicity (1)
- Expositionsmarker (1)
- External exposure assessment (1)
- Extrakorporale Dialyse (1)
- FACS (1)
- FCKW-Ersatzstoffe (1)
- FHK (1)
- FPG protein (1)
- FRAP (1)
- FRET sensors (1)
- Fabry Disease (FD) (1)
- Fettsucht (1)
- Fibromyalgie (1)
- Fibrose (1)
- Fischer 344 rats (1)
- Fl (1)
- FlAsH (1)
- Flow cytometry (1)
- Flugzeitmassenspektrometrie (1)
- Fluorescence (1)
- Fluorescence Correlation Spectroscopy (1)
- Fluorescence Microscopy (1)
- Fluorescence resonance energy transfer (1)
- Fluorescence-resonance-energy-transfer (1)
- Fluoreszenz <Motiv> (1)
- Fluoreszenzkorrelationsspektroskopie (1)
- Fluoreszenzmikroskopie (1)
- Fluorkohlenwasserstoffe (1)
- Fluoxetin (1)
- Fluoxetine (1)
- Folsäure (1)
- Frank-Starling-Gesetz (1)
- Fumonisin B1 (1)
- Fumonisine (1)
- Functional analyses (1)
- Fungizid (1)
- Förster Resonance Energy Transfer (1)
- G Protein (1)
- G Protein-Coupled Receptor (1)
- G beta gamma (1)
- G protein coupled receptor (GPCR) (1)
- G protein-coupled receptor (1)
- G protein-coupled receptor kinase (1)
- G protein-coupled receptor kinase 2 (GRK2) (1)
- G protein-gekoppelte Rezeptor Kinase 2 (GRK2) (1)
- G-Protein-gekoppelter-Rezeptor (1)
- G-Proteine (1)
- G-protein-coupled receptors (1)
- GABA-receptor complex (1)
- GC-MS (1)
- GC/MS (1)
- GIRK (1)
- GPCR dimerisation (1)
- GPCR signaling (1)
- GPCRs (1)
- GTP-bindende Proteine (1)
- Gastric carcinogenesis (1)
- Gb3 and lyso-Gb3 biomarkers (1)
- Gbetagamma-Untereinheiten (1)
- Gbetagamma-subunits (1)
- Gebärmutterhalskrebs (1)
- Gefäßentwicklung (1)
- Gegensatz (1)
- Genanalyse (1)
- Gene Transfer (1)
- Gene transfer (1)
- Genmutation (1)
- Genomische Instabilität (1)
- Genotoxicitiy (1)
- Genotyp (1)
- Genregulation (1)
- Gentoxikologie (1)
- Gi/o (1)
- Gilbert Syndrom (1)
- Gilbert´s Syndrome (1)
- Glatte Muskulatur (1)
- Glioblastom (1)
- Glucuronidation (1)
- Glukuronidierung (1)
- Glutathion S-Konjugat (1)
- Glutathione Stransferase (1)
- Glycerin-3-phosphat (1)
- Glycerinphosphate (1)
- Gq-Protein (1)
- Grün fluoreszierendes Protein (1)
- Guanin Nukleotid Austauschfaktor (1)
- Guaninnucleotid-Austauschfaktoren (1)
- Guanylatcyclase (1)
- HAD-Phosphatasen (1)
- HCM (1)
- HCN channel (1)
- HCN-Kanal (1)
- HFC245fa (1)
- HIPEC therapy (1)
- HIV (1)
- HIV infection (1)
- HPLC-MS/MS method (1)
- Hals-Nasen-Ohren-Tumor (1)
- Harn (1)
- Hauptkomponentenanalyse (1)
- HeLa cells (1)
- Hemmung der Proliferation schnell wachsender Krebszellen (1)
- Herpesviren (1)
- Herzfrequenz (1)
- Herzmuskelzelle (1)
- Herzrhythmusstörung (1)
- Hietzeschockprotein (1)
- High-thropughput screening (1)
- High-throughput screening (1)
- Hintergrund-DNA-Schaden (1)
- Hochdurchsatz-Screening (1)
- Hoechst 33258 dye (1)
- Homocystein (1)
- Hsp90 (1)
- Human (1)
- Human platelets (1)
- Humane Hämatopoetische Stammzellen (1)
- Hybridoma (1)
- Hydroxylradikal (1)
- Hyperinsulinämie (1)
- Hypernephrom (1)
- Hypertension (1)
- Hyperthermie (1)
- Hypertrophische Herzmuskelkrankheit (1)
- Häm (1)
- Hämatopoese (1)
- Hämodiafiltration (1)
- Hämoglobinaddukte (1)
- I1 Imidazolin Bindungsstelle (1)
- I1 imidazoline binding site (1)
- Immunization (1)
- Immunkardiomyopathie (1)
- Immunoblot (1)
- Immunologie (1)
- In vitro testing (1)
- In vitro toxicity testing (1)
- In vivo (1)
- In-silico Modell (1)
- Inflammation (1)
- Inhibitor (1)
- Interferenz (1)
- Inward Rectification (1)
- Ischemia/reperfusion (1)
- Janus-Aktivität (1)
- K + -channels (1)
- Kaffee (1)
- Kalzium (1)
- Kandidatengene (1)
- Kaninchen (1)
- Kardiomoyzyten (1)
- Kardiomyozyt (1)
- Kardiomyozyten (1)
- Karzinogenese (1)
- Katecholamine (1)
- Kidneys (1)
- Kinase signaling (1)
- Kinder (1)
- Kinetochore (1)
- Kinetochores (1)
- Klassifizierung (1)
- Klastogene (1)
- Knockout (1)
- Kognitive Beeinträchtigung (1)
- Kombination (1)
- Konformationsänderung (1)
- Kopf-Hals-Tumor (1)
- Krebs <Medizin> (1)
- L5178Y-Zellen (1)
- LC-MS/MS (1)
- LIMK (1)
- LPS (1)
- LTB4 receptor (1)
- Latrophilin (1)
- Lebendzellmikroskopie (1)
- Leukocyte/endothelium interaction (1)
- Ligand <Biochemie> (1)
- Liganden (1)
- Lipidom (1)
- Lipidomics (1)
- Liver (1)
- Lung (1)
- Lymphozyt (1)
- Lymphozyten (1)
- Lysosom (1)
- MAO-Hemmer (1)
- MAP (1)
- MAP-kinase (1)
- MDA-MB-231 breast cancer cells (1)
- MDA-MB-231-Brustkrebszellen (1)
- MIBG (1)
- MMQ cells (1)
- MMR-Reparatur (1)
- Magenkrebs (1)
- MammaJian mutagenicity test (1)
- Mammakarzinom (1)
- Map-kinase (1)
- Massenspektrometrie (1)
- Mastzelle (1)
- Matrix-Metalloprotease (1)
- Matrix-Metalloproteinase (1)
- Mauslymphomtest (1)
- Mauslymphomzellen (1)
- Mauslymphomzellen L5178Y (1)
- Mechanism of action (1)
- Melanocortin 4 receptor (MC4R) (1)
- Melanocyte stimulating hormones MSH (1)
- Melanoma (1)
- Melanomzelllinien (1)
- Membranrezeptor (1)
- Merkaptolaktat (1)
- Merkaptursäure (1)
- Metabolic activation (1)
- Metabolism (1)
- Metabolism saturation (1)
- Metabolite von Morphin (1)
- Metabolites of morphine (1)
- Metabolom (1)
- Metabolomics (1)
- Metabonomix (1)
- Methode der partiellen kleinsten Quadrate (1)
- Methylierung (1)
- Methylphenidat (1)
- Methymethansulfonat (1)
- Microcirculation (1)
- Micronucleus formation (1)
- Micronucleus test (1)
- Microscopy (1)
- Mikrokernfrequenz (1)
- Mikrokernfrequenzanalyse (1)
- Mikronukleus-Assay (1)
- Mineralokortikoidrezeptor (1)
- Mitosis (1)
- Mobiles Endgerät (1)
- Mobilfunk (1)
- Mobilfunkstrahlung (1)
- Molekularpharmakologie (1)
- Monoaminoxidase (1)
- Morphin (1)
- Multivariate Analyse (1)
- Mundschleimhaut (1)
- Mundschleimhautzellen (1)
- Mutagen (1)
- Mutagenicity (1)
- Mutagenicity assay (1)
- Mutagenitätstest (1)
- Mutagens (1)
- Mutation (1)
- Mutation assay (1)
- Mykotoxin (1)
- Myocard (1)
- Myofilament (1)
- Myosin (1)
- N-methyl-N-nitrosourea (1)
- N1E 115 cells (1)
- NADPH oxidase (1)
- NHERF (1)
- NOF (1)
- Na/H-Austauscher (1)
- Na/H-exchanger (1)
- Natrium-Calcium-Austauscher (1)
- Nebenniere (1)
- Neomycin Resistance (1)
- Nephrotoxicity (1)
- Nervennetz (1)
- Nervenzelle (1)
- Neuronale (1)
- Niereninsuffizienz (1)
- Nierenschädigung (1)
- Nierenschädigungsmarker (1)
- Nierenzellkarzinom (1)
- Nitrosation (1)
- Nitrosativer Stress (1)
- Nitrosierung (1)
- No:cGMP-Signalling (1)
- No:cGMP-Signalweg (1)
- Nrf 2 (1)
- OXPHOS (1)
- Opiatrezeptor (1)
- Ortspezifische Mutagenese (1)
- Oxidative Stress (1)
- Oxidative stress (1)
- Oxygen radical (1)
- PBPK/PBTK model (1)
- PDE-Hemmung (1)
- PDE2 (1)
- PKA (1)
- PLCβ3 (1)
- PLP (1)
- PMCA (1)
- PTH1R (1)
- Paclitaxel (1)
- Partial Agonists (1)
- Partialagonismus (1)
- Passivrauchen (1)
- Patulin (1)
- Peptides (1)
- Perforine (1)
- PhD thesis pharmacology (1)
- Pharmakogenetik (1)
- Phenobarbital (1)
- Phosducin-like Proteine (1)
- Phosducin-ähnliches protein (PhLP) (1)
- Phosphodiesterasen (1)
- Phosphoglykolat (1)
- Phosphoglykolat-Phosphatase (1)
- Phospholipase C (1)
- Phosphorylierung (1)
- Photoaffinity labelling (1)
- Physiologically based kinetic models (1)
- Physiologie (1)
- Phytohormone (1)
- Phänotyp (1)
- Phäochromozytomzellen (1)
- Plasmamembran-Kalzium-ATPase (1)
- Plazenta (1)
- Pointmutation (1)
- Pore (1)
- Pore formation (1)
- Pore-formation (1)
- Porenbildung (1)
- Prevalence (1)
- Prognostic impact (1)
- Prolactin (1)
- Propenderivate (1)
- Proteasom (1)
- Protein (1)
- Protein Folding (1)
- Protein Interaction (1)
- Protein binding (1)
- Protein coding (1)
- Protein-Protein-Wechselwirkung (1)
- Proteinaddukte (1)
- Proteinbindung (1)
- Proteinfaltung (1)
- Proteinkinase A (1)
- Proteinkinase C (1)
- Proteinkinase CK2 (1)
- Proteintyrosinphosphatase (1)
- Proteolyse (1)
- Protonen-NMR-Spektroskopie (1)
- Pyridoxal phosphate phosphatase (1)
- Pyridoxalphosphat Phosphatase (1)
- Quantitative risk assessment (1)
- RAMP (1)
- RGS2 (1)
- RNA degradation (1)
- RNS-Interferenz (1)
- ROS (1)
- Radiation inactivation (1)
- Radicals (1)
- Radioligand binding - 86Rb + -efflux (1)
- Radioligands (1)
- Radioligauds (1)
- Radiosensibilisierung (1)
- Raf Kinase Inhibitor Protein (RKIP) (1)
- Raf1 (1)
- Raman micro-spectroscopy (1)
- Rat Iiver microsomes (1)
- Rat liver peroxisome (1)
- Ratte (1)
- Raucher (1)
- ReAsH (1)
- Reactive intermediates (1)
- Reaktive Sauerstoffspezies (1)
- Reaktive Zwischenstufe (1)
- Real-Time quantitative PCR (1)
- Receptor (1)
- Receptor dynamics (1)
- Refraktärzeit (1)
- Regulator of G protein signaling 2 (1)
- Renin-Angiotensin-Aldosteron-System (1)
- Renin-Angiotensin-System (1)
- Resistenzentwicklung (1)
- Resveratrol (1)
- Retinales S-Antigen (1)
- Rgs2 (1)
- Rho-GTPasen (1)
- Rho-Proteine (1)
- Riddelliin (1)
- Riot control agents (1)
- Risikobewertung (1)
- Risk assessment (1)
- Risk estimation (1)
- Risk-factors (1)
- SCN5a (1)
- ST-elevation myocardial infarction (1)
- SUMO (1)
- Salmonella typhimurium (1)
- Schwesterchromatidenaustausche (1)
- Sekunde (1)
- Selenmangel (1)
- Senecionin (1)
- Seneciphyllin (1)
- Sensitivity (1)
- Sensor (1)
- Short-term Carcinogenicity Test (1)
- Short-term tests (1)
- Signal transduction (1)
- Signalkette (1)
- Small RNA (1)
- Species Differences (1)
- Species differences (1)
- Spermatogenesis (1)
- Speziesunterschiede (1)
- Spironolacton (1)
- Spontaneous tumours (1)
- Src (1)
- Stable Transformation (1)
- Statin (1)
- Stickstoffmonoxid (1)
- Stickstoffoxidsynthase (1)
- Stoffwechsel (1)
- Strahlentherapie (1)
- Streptococcus pneumoniae (1)
- Streptomyces (1)
- Stress (1)
- Structureactivity relationship (1)
- Styrol (1)
- Substratspezifitätsschleife (1)
- Sudden Cardiac Death (1)
- Sulfonylharnstoffe (1)
- Sulforaphane (1)
- Sympathikus (1)
- Synergie (1)
- Synergismus (1)
- Systembiologie (1)
- Säugerzellen (1)
- Säugetiere (1)
- T cells (1)
- TCP-1 alpha (1)
- TIRF (1)
- TK6 cells (1)
- Tabakrauch (1)
- Target size (1)
- Tetrachlormethan (1)
- Tetracystein-Motive (1)
- Tetracystein-Motivee (1)
- Thebain (1)
- Theophylline (1)
- Thrombin (1)
- Thymidine glycol (1)
- Tiermodell (1)
- Time-of-flight (1)
- Toluene (1)
- Toxicokinetics (1)
- Toxikokinetik (1)
- Toxizitätstest (1)
- Transfection (1)
- Transgene Mäuse (1)
- Transgenes Mausmodell (1)
- Transgenic mice (1)
- Transgenic mouse (1)
- Transgenie mice (1)
- Transkription (1)
- Transkriptionsfaktoren (1)
- Trenbolone (1)
- Trifluorpropionsäure (1)
- Tritiated Water (1)
- Troponin (1)
- Tumorpromotion (1)
- Tumorzelle (1)
- Tumorzellproliferation (1)
- Tyrosin (1)
- Tyrosin phosphatase (1)
- UCP2 (1)
- UCP2-Protein (1)
- UGT1A1 (1)
- Ubiquitin (1)
- Unscheduled DNA synthesis (1)
- Urämische Toxine (1)
- Uterine tumors (1)
- VASP (1)
- Validierung (1)
- Valvular heart-desease (1)
- Venerologie (1)
- Vitamin B12 (1)
- Vitamin B6 (1)
- Vitamin B6 Metabolismus (1)
- Vitamin E Mangel (1)
- Vitamin-B6-Stoffwechsel (1)
- Volume distribution (1)
- WD 40 Repeat Proteins (1)
- Wachstum (1)
- Wachstumskonus (1)
- Water resources (1)
- Wirkstoff-Rezeptor-Bindung (1)
- Xanthines (1)
- YFP (1)
- Zell-Adhäsion (1)
- Zelladhäsion (1)
- Zelldifferenzierung (1)
- Zelllinie (1)
- Zellproliferationssteigerung (1)
- Zellskelett (1)
- Zellteilung (1)
- Zelltransport (1)
- Zellzykluskontrolle (1)
- Zigarettenrauch (1)
- Zyklopeptid (1)
- [3H]PIA binding (1)
- absorption (1)
- activation (1)
- active zone (1)
- acute slices (1)
- adduct (1)
- adenine (1)
- adenosine 3',5'-cyclic monophosphate (1)
- adenylate cyclase (1)
- adenylyl cyclase signaling cascade (1)
- adenylyl-cyclase isoforms (1)
- adhesion GPCR (1)
- adiponectin (1)
- adipose tissue (1)
- adrenal gland (1)
- adrenerg (1)
- adrenerge Rezeptoren (1)
- adrenergic (1)
- adrenergic receptors (1)
- adrenoceptor (1)
- adult ADHD (1)
- adult cardiac myocytes (1)
- advanced glycosylation end product (1)
- adverse outcome pathway (1)
- adverse outcome pathway (AOP) (1)
- aflatoxin (1)
- aflatoxin B1 (1)
- ageing (1)
- agonists (1)
- alkylating agent (1)
- alkylating agents (1)
- alkylation (1)
- allelic variant (1)
- allosteric modulation (1)
- alpha2 (1)
- alpha2-KO Maus (1)
- alpha2-KO mouse (1)
- alpha2-Rezeptor (1)
- alpha2-adrenerge Rezeptoren (1)
- alpha2-adrenergic receptors (1)
- alpha2-receptor (1)
- alternative methods (1)
- amine (1)
- amino acid (1)
- aneugens (1)
- angiotensin II (1)
- angiotensin II type 1a receptor (1)
- antagonists (1)
- anthocyanins (1)
- anti-Parkinson agents (1)
- anti-inflammatory agents (1)
- antibacterial/antiviral drug (1)
- antibodies (1)
- antibody/autoantibody (1)
- antimutagenicity (1)
- antioxidants (1)
- aortocaval fistula model (1)
- aromatic amides (1)
- arrhythmia (1)
- arrhythmogenesis (1)
- arsenite (1)
- assay (1)
- association (1)
- astrocytes (1)
- atopic eczema (1)
- atopische Erkrankungen (1)
- atrial natriuretic peptide (1)
- autophosphorylation of ERK1/2 (1)
- avaliação de risco (1)
- bacterial meningitis (1)
- base excision repair (incision activity) (1)
- benfotiamine (1)
- beta-adrenerge Rezeptoren (1)
- beta-adrenergic signal transduction (1)
- beta2-adrenoceptor knockout (1)
- beta3 CL 316,243 (1)
- binding affinity (1)
- bioactive compounds (1)
- biofilms (1)
- biology (1)
- biomarker of exposure (1)
- biomarkers (1)
- biosensor (1)
- biotransformation (1)
- bisphenol a (1)
- blood coagulation factor XIII (1)
- blood plasma (1)
- blood pressure (1)
- blood samples (1)
- bombyx mori (1)
- bone marrow (1)
- brain damage (1)
- brain membranes (1)
- buccal mucosa (1)
- caffeine (1)
- calcitonin gene-related peptide (1)
- calcium channel (1)
- calmodulin (1)
- carcinogenesis (1)
- cardiac magnetic resonance imaging (1)
- cardiac myocyte ; muscarinic K current ; G-protein ; Albumin ; serum (1)
- cardiac remodelling (1)
- cardiomyocyt (1)
- cardiomyocyte (1)
- cardiomyocytes (1)
- cardiomyopathy (1)
- cardiovascular diseases (1)
- casein kinase 2 (1)
- catecholamines (1)
- caveolae (1)
- caveolin-1 (1)
- cell adhesion (1)
- cell biology (1)
- cell fate (1)
- cell fusion (1)
- cell proliferation (1)
- cell staining (1)
- cell-cycle (1)
- cellular-trafficking (1)
- chalcone (1)
- checkpoints (1)
- chemotactic receptors (1)
- chemotaxis (1)
- child health (1)
- children (1)
- cholesterol depletion (1)
- cholesterol-dependent cytolysin (1)
- cholinesterase (1)
- cholinesterase inhibitors (1)
- chromaffin granulas (1)
- chromaffine Granulas (1)
- chromosomal damage (1)
- chronic heart failure (1)
- chronic kidney disease (1)
- chronical stress (1)
- chronischer Stress (1)
- chronophin (1)
- cis-2-Buten-1 (1)
- classification and labeling (1)
- clastogens (1)
- clonidine (1)
- co-culture (1)
- coated vesicles (1)
- coffee (1)
- cognitive impairment (1)
- coherent anti-Stokes Raman scattering (CARS) microscopy (1)
- comet assay analysis (1)
- compartments (1)
- conduction disease (1)
- conformational auto-epitope (1)
- conjugated mycotoxins (1)
- constitutive activity (1)
- contact lens (1)
- continuous (1)
- contractility (1)
- control of the cell cycle (1)
- coumarin (1)
- coupled (1)
- coupled receptor (1)
- covalent (1)
- covalent binding (1)
- creatinine (1)
- crystal structure (1)
- cyclic AMP (1)
- cyclic dipeptide (1)
- cyclic nucleotides such as cyclic adenosine monophosphate (1)
- cyclic peptides/cyclopeptides (1)
- cyclic-AMP (1)
- cyclic-gmp (1)
- cyclo-AMP (1)
- cyclopeptide therapy (1)
- cytochrome P450 2C9 (1)
- cytochrome P450s (1)
- cytochrome p450 (1)
- cytogenetic effects (1)
- cytokinesis-block micronucleus assay (1)
- cytome biomarkers (1)
- cytosol (1)
- cytotoxic (1)
- dCIRL (1)
- danio rerio (1)
- definition (1)
- dendritic spines (1)
- desensitization (1)
- detrusor muscle (1)
- diabetes (1)
- diagnosis (1)
- dicyclohexyl phthalate (1)
- diet (1)
- differentiation status (1)
- dilated cardiomyopathy with ataxia (1)
- disrupting chemicals (1)
- disruptor endócrino (1)
- dna damage (1)
- dna strand break (1)
- docking (1)
- domains (1)
- dopamine-beta-hydroxylase-promotor (1)
- dormancy (1)
- dose (1)
- dose response (1)
- down-regulation (1)
- drug (1)
- dualsteric ligands (1)
- dunce (1)
- eccentric hypertrophy (1)
- ecdysone (1)
- ectodomain cleavage (1)
- efficient intervention points (1)
- embryonic stem cell (1)
- end-stage renal disease (1)
- endocrine disruptor (1)
- endogenous (1)
- endothelial cells (1)
- energy-transfer (1)
- environm. tobacco smoke (1)
- environmental phenols (1)
- enzyme-linked immunoassays (1)
- epigenetics (1)
- estrogen receptor (1)
- estrogens (1)
- ethanol (1)
- etoposide (1)
- etox database (1)
- eugenol (1)
- exposição humana (1)
- exposure (1)
- extrapolation (1)
- fatty liver (1)
- fentanyl (1)
- fetal testis (1)
- fibrosis (1)
- fluorescence correlation spectroscopy (1)
- fluorescence detection (1)
- fluorescence imaging (1)
- fluorescence recovery after photobleaching (1)
- fluorescent probes (1)
- fluorocarbons (1)
- folic acid (1)
- food contact materials (1)
- food safety (1)
- food security (1)
- formyl peptides (1)
- fumonisin B1 (1)
- functional clustering (1)
- fungi (1)
- gastrointestinal cancer (1)
- genetics (1)
- genetischer Schadens (1)
- genomprotektiv (1)
- genotoxic (1)
- genotoxic agents (1)
- genotoxisch (1)
- genotoxische Agenzien (1)
- genotypes (1)
- genotyping (1)
- glucuronide (1)
- glutamate (1)
- glutathion S-conjugate (1)
- glycolytic flux control (1)
- gprotein (1)
- gravidez (1)
- growth (1)
- growth cone (1)
- guanine nucleotide exchange factor (1)
- hA<sub>3</sub>AR (1)
- hOCT1 (1)
- haematopoietic stem cells (1)
- halo olefines (1)
- haloacid dehalogenase (1)
- head and neck cancer (1)
- healing and remodelling processes (1)
- heart rate (1)
- heat shock protein (1)
- heme (1)
- hemodiafiltration (1)
- hemodialysis (1)
- hemodialysis patients (1)
- hemoglobin adducts (1)
- heterogeneous population (1)
- hiPSC-CM (1)
- hidden mycotoxins (1)
- histamine release (1)
- homeostasis (1)
- homocysteine (1)
- homodimerization (1)
- hormone receptors (1)
- huh6 (1)
- human (1)
- human A(3) (1)
- human biomonitoring (1)
- human exposure (1)
- human hematopoietic stem cells (1)
- human lung (1)
- hydrofluorocarbons (1)
- hypertonic solution (1)
- hypertrophy (1)
- identification (1)
- idiosyncratic drug toxicity (1)
- idiosynkratische Arzneistofftoxizität (1)
- impact pharmacogenetics (1)
- in vitro (1)
- in vivo (1)
- in-silico model (1)
- individual (1)
- indolylpyrimidylpiperazines (1)
- induced pluripotent stem cell cardiomyocytes (1)
- induced pluripotent stem cells (1)
- inducible transgene (1)
- induzierbares Transgen (1)
- induzierte Mutation (1)
- induzierte Phosphatasen MKP-1 und MKP-2 (1)
- inflammatory diseases (1)
- inhalation (1)
- inhibitor (1)
- inhibitors (1)
- insulin signaling (1)
- internalization (1)
- international union (1)
- intracellular calcium release (1)
- intracellular loop (1)
- intrinsic metabolism (1)
- ionic look (1)
- irradiation (1)
- ischemic stroke (1)
- isoproterenol (1)
- kardiale Hypertrophie (1)
- key event relationship (1)
- kinases (1)
- laminopathy (1)
- lamivudine (1)
- lasiocarpine (1)
- legislation (1)
- life (1)
- ligand binding (1)
- ligandenselektive Konformationen (1)
- lignaselective conformations (1)
- lipid rafts (1)
- lipidomics (1)
- listeriolysin O (1)
- live imaging (1)
- liver microsomes (1)
- living vells (1)
- long-read sequencing (1)
- lovastatin (1)
- lysosomal disruption (1)
- lysosomaler Overload (1)
- lösliche Guanylylcyclase (1)
- mTOR-inhibitor RAD-001 (1)
- maintenance of genomic integrity (1)
- male rats (1)
- mammalian cells (1)
- mammalian genomics (1)
- mao-inhibiters (1)
- marine sponges (1)
- markers of exposure (1)
- masked mycotoxins (1)
- mass spectrometry (1)
- matrix metalloproteinase (1)
- mechanotransduction (1)
- membrane (1)
- membrane transporters (1)
- memory B cells (1)
- mercaptolactic acid (1)
- meta-Iodbenzylguanidin (1)
- meta-iodobenzylguanidine (1)
- metabolites (1)
- metabolomics (1)
- metabotropic signalling (1)
- methyl methanesulfonate (1)
- methylation (1)
- miR-21 (1)
- microRNA-21 (1)
- micronucleus (1)
- micronucleus assay (1)
- micronucleus frequency (1)
- micronucleus- assay (1)
- microvessel permeability (1)
- mild (1)
- mismatch repair (1)
- mitochondria (1)
- mitochondrial DNA polymerase γ (1)
- mitotic catastrophe (1)
- mitotic disturbance (1)
- mixture models (1)
- mobil phone radiation (1)
- modelo PBPK/PBTK (1)
- modified mycotoxins (1)
- molecular biology (1)
- molecular dynamics (1)
- molecular modeling (1)
- molecular modelling (1)
- monoamine oxidase (1)
- mortality (1)
- mouse (1)
- mouse lymphoma L5178Y (1)
- mouse lymphoma cells (1)
- mouse models DNA damage (1)
- mucosa (1)
- multivariate analysis (1)
- multivariate data analysis (1)
- muscarinic acetylcholine receptor (1)
- muscarinic aceylcholine receptor (1)
- mutagen (1)
- mutant mice (1)
- mutation triggers (1)
- mycotoxin derivates (1)
- mycotoxin metabolites (1)
- mycotoxins (1)
- myocardium (1)
- myosin (1)
- n-hexyl phthalate (1)
- nanopore (1)
- natural (1)
- neocortex (1)
- neurodegenerative diseases (1)
- neuronal (1)
- neuronal dendrites (1)
- neurons (1)
- neutrophils (1)
- nicht additive Effekte (1)
- nitric oxide (1)
- nitric-oxide (1)
- nitrosation (1)
- nitrosative stress (1)
- nitroso compound (1)
- no (1)
- non-additive effects (1)
- noradrenaline (1)
- nutritional composition (1)
- o-Chlorobenzylidene malononitrile (1)
- occurrence (1)
- ochratoxin A (1)
- octopamine (1)
- oligomerization (1)
- opioid ligands (1)
- opioid receptor (1)
- optimal drug combination (1)
- optimal drug targeting (1)
- optimal pharmacological modulation (1)
- optimal treatment strategies (1)
- organ toxicity (1)
- ovarian cancer (1)
- oxidative Stressmarker (1)
- oxidative stress marker (1)
- p53 (1)
- paclitaxel (1)
- parathyroid hormone (1)
- parathyroid hormone 1 receptor (1)
- partial agonists (1)
- passive smoking (1)
- performance liquid-chromatography (1)
- peripheral nerve (1)
- peripheral-blood lymphocytes (1)
- periphere Lymphozyten (1)
- personalized treatment (1)
- perspectives (1)
- pharmacology (1)
- phenobarbitale (1)
- phenotyping (1)
- pheochromocytoma cells (1)
- phopohrylierungsdefizient (1)
- phosducin (1)
- phosducin-like protein (PhLP) (1)
- phosphoglycolate phosphatase (1)
- phosphoglycolatephosphatase (1)
- phosphoinositides (1)
- phosphorylation (1)
- photoaffinity labelling (1)
- phytohormones (1)
- placenta (1)
- plasma membrane (1)
- plasma membrane calcium ATPase (1)
- plötzlicher Herztod (1)
- pms2 (1)
- poly(ADP-ribosyl)ation (1)
- pore formation (1)
- pore-forming toxin (1)
- posttranslational modification (1)
- posttranslationale Modifikation (1)
- potent (1)
- pregnancy (1)
- primary aromatic amine (1)
- proliferation (1)
- protein (1)
- protein adducts (1)
- protein alkylation (1)
- protein design (1)
- protein-coupled receptors (1)
- protein-coupled-receptors (1)
- psoriasis (1)
- psychosocial stress (1)
- psychosozialer Stress (1)
- purine derivatives (1)
- pyridoxal phosphatase (1)
- pyridoxal phosphate (1)
- pyrrolizidine alkaloids (1)
- quantitative assessments (1)
- radii (1)
- radiofrequency radiation (1)
- radioligand (1)
- radioligand binding (1)
- radiosensibilisation (1)
- rat pheochromocytoma cells (1)
- rats (1)
- reactive metabolites (1)
- reaktive Metabolite (1)
- reaktive Sauerstoffspezies (1)
- receptor (1)
- receptor binding (1)
- receptor pharmacology (1)
- receptor solubilization (1)
- receptor-G protein coupling (1)
- receptor-G protein coupling. (1)
- red blood cells (1)
- reduction of ERK1/2 phosphorylation (1)
- reduction of cells proliferation (1)
- regulation (1)
- relaxation (1)
- renal toxicity (1)
- repeated dose (1)
- reproductive and developmental toxicity (1)
- resistance (1)
- rezeptorvermittelte Endozytose (1)
- risk (1)
- risk-assesment (1)
- sGC (1)
- second extracellular loop (1)
- senecionine (1)
- seneciphylline (1)
- sensor (1)
- sensory physiology (1)
- serum (1)
- sex (1)
- sexual development (1)
- signaling microdomain (1)
- simulated digestion (1)
- single-molecule imaging (1)
- single-molecule microscopy (1)
- sister chromatid exch. (1)
- solid-phase extraction (1)
- solubilization (1)
- soluble guanylyl cyclase (1)
- sponges (1)
- spontaneously hypersensitive-rats (1)
- stabile Transfektion (1)
- stable transfection (1)
- staphilococci (1)
- statins (1)
- stomach (1)
- streptomyces (1)
- sub-Saharan Africa (1)
- sublinear (1)
- subtypes (1)
- sugars (1)
- sulfonylurea (1)
- susceptibility (1)
- synapses (1)
- synaptic plasticity (1)
- synergism (1)
- tMCAO (1)
- tandem mass-spectrometry (1)
- targets (1)
- terminale Niereninsuffizienz (1)
- testosterone production (1)
- tetrafluoropropene (1)
- therapeutic potential (1)
- thrombin (1)
- thyroid hormone (1)
- tierversuchsfrei (1)
- tissue (1)
- tolbutamide substrate (1)
- toxicity testing (1)
- toxicocinética (1)
- toxicokinetics (1)
- toxicology (1)
- trans-1 (1)
- trans-Golgi network (1)
- transcription (1)
- transgene Ratten (1)
- transgene rats (1)
- transgenic (1)
- transgenic animals (1)
- transgenic mice (1)
- triazolotriazine derivatives (1)
- trifluoropropionic acid (1)
- tuber (1)
- tumour (1)
- tumourpromotion (1)
- tyrosine phosphatase (1)
- ubiquitin (1)
- ultrastructure (1)
- urea (1)
- variocosities (1)
- vascular smooth muscle cells (1)
- vasculogenesis (1)
- vaskuläre glatte Muskelzellen (1)
- vav2 (1)
- vessel (1)
- vitamin B6 (1)
- vitamin b12 (1)
- vitamin-D-receptor (1)
- volume overload (1)
- warfarin polymorphisms (1)
- weight of evidence (1)
- yellow fluorescent protein (1)
- zweite extrazelluläre Domäne (1)
- µ-Opioid receptor (1)
- Östrogen (1)
- ß-adrenerge Rezeptoren (1)
- ß-adrenerge Signaltransduktion (1)
- ß-adrenergic Receptors (1)
- β-adrenergic receptors (1)
- β1-adrenoceptor/β1-adrenergic receptor (1)
- βAR (1)
- γ-H2AX (1)
Institute
- Institut für Pharmakologie und Toxikologie (399) (remove)
Sonstige beteiligte Institutionen
- Institut für Biopsychologie, Universität Dresden (1)
- Johns Hopkins School of Medicine (1)
- Johns Hopkins School of Medicine, Baltimore, MD, U.S. (1)
- Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V. (1)
- Max Delbrück Center for Molecular Medicine (1)
- Max-Delbrück-Center für molekulare Medizin, Berlin (1)
- Pharmakologie, Universität Bonn (1)
- Pharmazie, Universität Mailand (1)
- Universitätsklinikum Düsseldorf, Institut für Toxikologie (1)
Adenosine receptor ligands: coumarin−chalcone hybrids as modulating agents on the activity of hARs
(2020)
Adenosine receptors (ARs) play an important role in neurological and psychiatric disorders such as Alzheimer's disease, Parkinson's disease, epilepsy and schizophrenia. The different subtypes of ARs and the knowledge on their densities and status are important for understanding the mechanisms underlying the pathogenesis of diseases and for developing new therapeutics. Looking for new scaffolds for selective AR ligands, coumarin–chalcone hybrids were synthesized (compounds 1–8) and screened in radioligand binding (hA\(_1\), hA\(_{2A}\) and hA\(_3\)) and adenylyl cyclase (hA\(_{2B}\)) assays in order to evaluate their affinity for the four human AR subtypes (hARs). Coumarin–chalcone hybrid has been established as a new scaffold suitable for the development of potent and selective ligands for hA\(_1\) or hA\(_3\) subtypes. In general, hydroxy-substituted hybrids showed some affinity for the hA\(_1\), while the methoxy counterparts were selective for the hA\(_3\). The most potent hA\(_1\) ligand was compound 7 (K\(_i\) = 17.7 µM), whereas compound 4 was the most potent ligand for hA\(_3\) (K\(_i\) = 2.49 µM). In addition, docking studies with hA\(_1\) and hA\(_3\) homology models were established to analyze the structure–function relationships. Results showed that the different residues located on the protein binding pocket could play an important role in ligand selectivity.
Adenosine receptor agonists: Synthesis and biological evaluation of 1-deaza analogues of adenosine
(1988)
In a search for more selective A\(_1\) adenosine receptor agonists, N\(^6\)-[(R)-(-)-1-methyl-2-phenethyl]-1-deazaadenosine (1-deaza-R-PIA, 3a), N\(^6\)-cyclopentyl-1-deazaadenosine (1-deazaCPA, 3b), N\(^6\)-cyclohexyl-l-deazaadenosine (1-deazaCHA, Sc), and the corresponding 2-chloro derivatives 2a-c were synthesized from 5,7-dichloro-3-ß-D-ribofuranosyl-3Himidazo[ 4,5-b]pyridine (1). On the other band, N-ethyl-1'-deoxy-1'-(1-deaza-6-amino-9H-purin-9-yl)-ß-D-ribofuranuronamide (1-deazaNECA, 10) was prepared from 7-nitro-3-ß-D-ribofuranosyl-3H-imidazo[4,5-b]pyridine (4), in an attempt to find a more selective A\(_2\) agonist. The activity of all deaza analogues at adenosine receptors has been determined in adenylate cyclase andin radioligand binding studies. 1-DeazaNECA (10) proved tobe a nonselective agonist at both subtypes of the adenosine receptor. It is about 10-fold less active than NECA but clearly more active than the parent compound 1-deazaadenosine as an inhibitor of platelet aggregation and as a stimulator of cyclic AMP accumulation. The N\(^6\)-substituted 1-deazaadenosines largely retain the A\(_1\) agonist activity of their parent compounds, but lose some of their A\(_2\) agonist activity. This results in A\(_1\)-selective compounds, of which N\(^6\)cyclopentyl- 2-chloro-1-deazaadenosine (1-deaza-2-Cl-CPA, 2b) was identified as the most selective agonist at A\(_1\) adenosine receptors so far known. The activity of all 1-deaza analogues confirms that the presence of the nitrogen atom at position 1 of the purine ring is not critical for A\(_1\) receptor mediated adenosine actions.
Recently, it was shown that MDA-MB-231 breast cancer cells express very high levels of the A2BAR as the sole adenosine receptor subtype, and stimulation of the A2BAR in MDA-MB-231 cells triggers an unusual inhibitory signal on ERK1/2 phosphorylation. The ERK1/2 pathway is reported to be associated with the control of growth, proliferation and differentiation of cells and as such might serve as a promising target for tumor treatment. The present study investigated signaling mechanisms involved in linking A2BAR to ERK1/2 phosphorylation in MDA-MB-231 cells. The A2BAR mediated reduction of ERK1/2 phosphorylation and of proliferation of MDA-MB-231 cell is in good agreement with previous results from (Dubey et al., 2005). These observations provide support to the hypothesis that activation of A2BAR could attenuate the growth of some types of cancer cell and argue against a stimulation of proliferation resulting from the activation of A2BAR as discussed by (Fernandez-Gallardo et al., 2016). AC activation by forskolin has recently been shown to enhance the activity of the chemotherapeutic agent doxorubicin in TNBC cells via a mechanism dependent on the PKA-mediated inhibition of ERK1/2 phosphorylation. Furthermore, forskolin also increased the sensitivity of MDA-MB-231 and MDA-MB-468 triple negative breast cancer cells to 5-fluorouracil and taxol (Illiano et al., 2018), and sustains the evidence of anticancer activity mediated by cAMP/PKA-mediated ERK1/2 inhibition. Similar to these studies, a reduced amount of pERK1/2 was also observed after stimulation of AC with FSK, application of cAMP-AM or inhibition of PDE-4. The inhibition of ERK1/2 phosphorylation was mimicked by UTP and abolished with the PLC inhibitor U73122 or by chelating intracellular Ca2+ with BAPTA-AM. These results point to an important role for both cAMP and Ca2+ signaling in the pathway leading to a decrease in ERK1/2 phosphorylation. This study encourages the idea that A2BAR could be used as target in cancer therapy. But A2BAR did not only stimulate signaling cascades associated with cell survival and proliferation reduction, but also key phases relevant in angiogenesis like Ca2+ mobilization (Kohn et al., 1995). Whereas the potency toward AC and Ca2+ are similar for the diverse agonists, the potency to promote ERK1/2 reduction is much higher. Interestingly, the proliferation of MDA-MB-231 cells is inhibited by low nanomolar agonist concentration which is inactive in Ca2+ mobilization. This means that it is certainly possible to reduce the proliferation without promoting angiogenesis. LUF6210 is particularly interesting when considering that it preferentially stimulates a reduction in ERK1/2 phosphorylation over Ca2+ and therefore may not promote angiogenesis. LUF6210 is therapeutically appealing as adjuvant in treatment of cancer. Given that stimulation of AC can activate a reduction of ERK1/2 phosphorylation and proliferation in cancer cells, agonist bias toward Gs-AC-PKA-mediated ERK1/2 inhibition represent a potential therapy of various malignancies. The fact that the reduction of ERK1/2 phosphorylation followed by reduced proliferation observed in MDA-MB-231 cells were mediated by the activation of the A2BAR illustrates the importance of this receptor subtype in cancer. A2BARs must be considered as a key factor in cancer treatment and deserve attention for the development of new therapeutic strategies.
The A\(_{2A}\) adenosine receptor (A\(_{2A}\)AR) is one of the four subtypes activated by nucleoside adenosine, and the molecules able to selectively counteract its action are attractive tools for neurodegenerative disorders. In order to find novel A\(_{2A}\)AR ligands, two series of compounds based on purine and triazolotriazine scaffolds were synthesized and tested at ARs. Compound 13 was also tested in an in vitro model of neuroinflammation. Some compounds were found to possess high affinity for A\(_{2A}\)AR, and it was observed that compound 13 exerted anti-inflammatory properties in microglial cells. Molecular modeling studies results were in good agreement with the binding affinity data and underlined that triazolotriazine and purine scaffolds are interchangeable only when 5- and 2-positions of the triazolotriazine moiety (corresponding to the purine 2- and 8-positions) are substituted.
G-protein-coupled receptors (GPCRs) represent one of the most important classes of drug targets. The discovery of new GCPR therapeutics would greatly benefit from the development of a generalizable high-throughput assay to directly monitor their activation or de-activation. Here we screened a variety of labels inserted into the third intracellular loop and the C-terminus of the alpha(2 Lambda)-adrenergic receptor and used fluorescence (FRET) and bioluminescence resonance energy transfer (BRET) to monitor ligand-binding and activation dynamics. We then developed a universal intramolecular BRET receptor sensor design to quantify efficacy and potency of GPCR ligands in intact cells and real time. We demonstrate the transferability of the sensor design by cloning beta(2)-adrenergic and PTH1-receptor BRET sensors and monitored their efficacy and potency. For all biosensors, the Z factors were well above 0.5 showing the suitability of such design for microtiter plate assays. This technology will aid the identification of novel types of GPCR ligands.
Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2'-deoxyguanosine (8-oxodG), 5-hydroxy-2'-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.
Two forms of a DNA polymerase have been purified from microplasmodia of Physarum polycephalum by poly(ethyleneimine) precipitation and chromatography on DEAE-Sephacel, phosphocellulose, heparin Sepharose, hydroxyapatite, DNA-agarose, blue-Sepharose. They were separated from DNA polymerase cx on phosphocellulose and from each other on heparin-Sepharose. Form HS1 enzymewas 30-40% pure and form HS2 enzyme 60% with regard toprotein contents of the preparations. Form HS2 enzymewas generated from form HS1 enzyme on prolonged standing of enzyme preparations. The DNA polymerases were obtained as complexes of a 60-kDa protein associated with either a 135-kDa (HS1) or a 110-kDa (HS2) DNA-polymerizing polypeptidein a 1:1 molar stoichiometry. The biochemical function of the 60-kDa protein remained unknown. The complexes tended to dissociate during gradient centrifugation and during partition chromatography as weil as during polyacrylamide gradient gel electrophoresis under nondenaturing conditions at high dilutions of samples. Both forms existed in plasmodia extracts, their proportions depending on several factors including those which promoted proteolysis. The DNA polymerases resembled eucaryotic DNA polymerase ß by several criteria and were functionally indistinguishable from each other. It is suggested that lower eucaryotes contain repair DNA polymerases, which are similar to those of eubacteria on a molecular mass basis.
In the inhalation system described an animal can be kept in the same atmosphere of a 2-liter desiccator for up to 24 h. The expired carbon dioxide is adsorbed with soda lime and the resulting reduced pressure is balanced by a supply of oxygen also used for the inflow of the chemical to be investigated. Urine and faeces can be collected ~eparately and the system allows a periodical control of the concentration of the chemical by sampling the air with needle and syringe.
Neben der Chemotherapie ist heutzutage auch die Hyperthermie-Behandlung eine wichtige Säule der antitumorösen Therapie. Während der sogenannten HIPEC Therapie (Hypertherme intraperitoneale Chemoperfusion) werden die beiden Arten der Therapieformen kombiniert und in der klinischen Praxis erfolgreich angewendet. Genauere Kenntnisse über die zu Grunde liegenden toxikologischen in-vitro Mechanismen könnten zu neuen Möglichkeiten in der klinischen Anwendung führen. In unserer Arbeit untersuchten wir verschiedenen Tumorzelllinien (HT29,CaCo-2,HCT116,HaCaT) in Kombination mit Cisplatin und Hyperthermie mit verschiedenen Methoden, wie zum Beispiel Mikrokerntest, Comet-Assay, Durchflusszytometrie, Vitalitätstest und mikroskopischen Analysen. Unsere Ergebnisse führten uns zu der Hypothese, dass Hyperthermie alleine zu einer sogenannte mitotic catastrophe führt und zum Absterben der Tumorzellen. Im Gegensatz dazu zeigten Tumorzellen, welche mit Cisplatin alleine oder auch in Kombination mit Hyperthermie nicht in die Mitose eintreten und daher nicht durch Apoptose in den Zelltod gehen.
The properties of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as an antagonist ligand for A\(_1\) adenosirre receptors were examined and conipared with other radioligands for this receptor. DPCPX competitively antagonized both the inhibition of adenylate cyclase activity via A\(_1\) adenosirre receptors and the stimulationvia A\(_2\) adenosirre receptors. The K\(_i\)-values of this antagonism were 0.45 nM at the A\(_1\) receptor of rat fat cells, and 330 nM at the A\(_2\) receptor of human platelets, giving a more than 700-fold A\(_1\)-selectivity. A similar A\(_1\)-selectivity was determined in radioligand binding studies. Even at high concentrations, DPCPX did not significantly inhibit the soluble cAMPphosphodiesterase activity of human platelets. [\(^3\)H]DPCPX (105 Ci/mmol) bound in a saturable manner with high affinity to A\(_1\) receptors in membranes of bovine brain and heart, and rat brain and fat cells (K\(_D\) -values 50-190 pM). Its nonspecific binding was about 1% of total at K\(_D\) , except in bovine myocardial membranes (about 10%). Binding studies with bovine myocardial membranes allowed the analysis of both the high and low agonist affinity states of this receptor in a tissue with low receptor density. The binding properties of [\(^3\)H]DPCPX appear superior to those of other agonist and antagonist radioligands for the A\(_1\) receptor.
lt is known that 5-azacytidine (5-AC) induces tumors in several organs of rats and mice. The mechanisms of these effects are still poorly understood although it is known that 5-AC can be incorporated into DNA. Furthermore, it can inhibit DNA methylation. The known data on its clastogenic andjor gene mutation-inducing potential are still controversial. Therefore, we have investigated the kinds of genotoxic effects caused by 5-AC in Syrian hamster embryo (SHE) fibroblasts. Three different endp6ints (micronucleus formation, unscheduled DNA synthesis (UDS) and cell transforrnation) were assayed under similar conditions of metabolism and dose at target in this cell system. 5-AC induces morphological transformation of SHE cells, but not UDS. Therefore, 5-AC does not seem to cause repairable DNA lesions. Furthermore, our studies revealed that 5-AC is a potent inducer of mkronuclei in the SHE system. Immunocytochemical analysis revealed that a certain percentage of these contain kinetochores indicating that 5-AC may induce both clastogenic events and numerical chromosome changes.
2-Chloro-N\(^6\)-cyclopentyladenosine: a highly selective agonist at A\(_1\) adenosine receptors
(1988)
2-Chloro-N\(^6\)-cyclopentyladenosine (CCPA) was synthesized as a potential high affinity ligand for At adenosine receptors. Binding of [\(^3\)H]PIA to A1 receptors of rat brain membranes was inhibited by CCP A with a Ki-value of 0.4 nM, compared to a Ki-value of 0.8 nM for the parent compound N\(^6\)-cyclopentyladenosine (CPA). Binding of [\(^3\)H]NECA to A\(_2\) receptors of rat striatal membranes was inhibited with a Ki-value of 3900 nM, demonstrating an almost 10,000-fold A\(_1\)-selectivity of CCPA. CCP A inhibited the activity of rat fat cell membrane adenylate cyclase, a model for the A\(_1\) receptor, with an IC\(_{50}\)-value of 33 nM, and it stimulated the adenylate cyclase activity of human platelet membranes with an EC\(_{50}\)-value of 3500 nM. The more than 100-fold A\(_1\)-selectivity compares favourably with a 38-fold selectivity of CPA. Thus, CCPA is an agonist at A\(_1\) adenosine receptors with a 4-fold higher selectivity and 2-fold higher affinity than CPA, and a considerably higher selectivity than the standard At receptor agonist R-N\(^6\) -phenylisopropyladenosine (R-PIA). CCP A represents the agonist with the highest selectivity for A\(_1\) receptors reported so far.
The tritiated analogue of 2-chloro-N6-cyclopentyladenosine (CCPA), an adenosine derivative with subnanomolar affinity and a 10000-fold selectivity for A1 adenosine receptors, has been examined as a new agonist radioligand. [3H]CCP A was prepared with a specifi.c radioactivity of 1.58 TBqjmmol ( 43 Ci/mmol) and bound in a reversible manner to A1 receptors from rat brain membranes with a high affinity K0 -value of 0.2 nmol/1. In the presence of GTP a K0 -value of 13 nmol/1 was determined for the low affinity state for agonist binding. Competition of several adenosine receptor agonists and antagonists for [3H]CCPA binding to rat brain membranes confrrmed binding to an A1 receptor. Solubilized A1 receptors bound [3H]CCPA with similar affinity for the high affinity state. At solubilized receptors a reduced association rate was observed in the presence of MgC12, as has been shown for the agonist [ 3H]N6-phenylisopropyladenosine ([3H]PIA). [3H]CCPA was also used for detection of A1 receptors in rat cardio myocyte membranes, a tissue with a very low receptor density. A K0 -value of 0.4 nmol/1 and a Bmax-value of 16 fmol/ mg protein was determined in these membranes. In human platelet membranes no specific binding of [3H]CCPA was measured at concentrations up to 400 nmoljl, indicating that A2 receptors did not bind [3H]CCPA. Based on the subnanomolar affinity and the high selectivity for A1 receptors [ 3H]CCPA proved to be a useful agonist radioligand for characterization of A 1 adenosine receptors also in tissues with very low receptor density.
In the search for more selective A2-receptor agonists and on the basis that appropriate substitution at C2 is known to impart selectivity for A\(_2\) receptors, 2-alkynyladenosines 2a-d were resynthesized and evaluated in radioligand binding, adenylate cycla.se, and platelet aggregation studies. Binding of [\(^3\)H]NECA to A\(_2\) receptors of rat striatal membranes was inhibited by compounds 2a-d with K\(_i\) values ranging from 2.8 to 16.4 nM. 2-Alkynyladenosines also exhibited high-affmity binding at solubilized A\(_2\) receptors from human platelet membranes. Competition of 2-alkynyladenosines 2a-d for the antagonist radioligand [\(^3\)H]DPCPX and for the agonist [\(^3\)H]CCPA gave K\(_i\) values in the nanomolar range, and the compounds showed moderate A\(_2\) selectivity. In order to improve this selectivity, the correaponding 2-alkynyl derivatives of adenosine-5'-N-ethyluronamide 8a-d were synthesized and tested. A\(_1\) expected, the 5'-N-ethyluronamide derivatives retained the A\(_2\) affinity whereas the A\(_1\) affinity was attenuated, resulting in an up to 10-fold increase in A\(_2\) selectivity. A similar patternwas observed in adenylate cyclase assays andin platelet aggregation studies. A 30- to 45-fold selectivity for platelet A\(_2\) receptors compared to A\(_1\) receptors was found for compounds 8a-c in adenylate cyclase studies.
Tbe 2',3'-dideoxy analogue of the potent A\(_1\) receptor agonist, N\(^6\)-cyclohexyladenosine (CHA), was synthesized as a potential antagonist for the A\(_1\) adenosine receptor. In sturlies on adenylate cyclase 2',3'-dideoxy-N\(^6\)-cyclohexyladenosine (ddCHA) did not show agonist properties at A\(_1\) or at A\(_2\) receptors. However, it antagonized the inhibition by R-PIA of adenylate cyclase activity of fat cell membranes via A\(_1\) receptors with a K\(_i\) value of 13 \(\mu\)M. ddCHA competed for the binding of the selective A1 receptor antagonist, [\(^3\) HJ8-cyclopentyl-1,3-dipropylxantbine ([\(^3\)H]DPCPX), to rat brain membranes with a K\(_i\) value of 4.8 \(\mu\)M; GTP did not affect the competition curve. In contrast to the marked stereoselectivity of the A\(_1\) receptor for the cx- and the natural ß-anomer of adenosine, the cx-anomer of ddCHA showed a comparable affinity for the A\(_1\) receptor (K\(_i\) value 13.9 \8\mu\)M). These data indicate that the 2'- and 3'-hydroxy groups of adenosine and its derivatives are required foragonist activity at and high affinity binding to A\(_1\) adenosine receptors and for the distinction between the cx- and ß-forms.
1,25-dihydroxyvitamin D3 (1,25D3) was reported to induce premature organismal aging in fibroblast growth factor-23 (Fgf23) and klotho deficient mice, which is of main interest as 1,25D3 supplementation of its precursor cholecalciferol is used in basic osteoporosis treatment. We wanted to know if 1,25D3 is able to modulate aging processes on a cellular level in human mesenchymal stem cells (hMSC). Effects of 100 nM 1,25D3 on hMSC were analyzed by cell proliferation and apoptosis assay, beta-galactosidase staining, VDR and surface marker immunocytochemistry, RT-PCR of 1,25D3-responsive, quiescence-and replicative senescence-associated genes. 1,25D3 treatment significantly inhibited hMSC proliferation and apoptosis after 72 h and delayed the development of replicative senescence in long-term cultures according to beta-galactosidase staining and P16 expression. Cell morphology changed from a fibroblast like appearance to broad and rounded shapes. Long term treatment did not induce lineage commitment in terms of osteogenic pathways but maintained their clonogenic capacity, their surface marker characteristics (expression of CD73, CD90, CD105) and their multipotency to develop towards the chondrogenic, adipogenic and osteogenic pathways. In conclusion, 1,25D3 delays replicative senescence in primary hMSC while the pro-aging effects seen in mouse models might mainly be due to elevated systemic phosphate levels, which propagate organismal aging.