@article{WagnerBerteroNickeletal.2020,
  author    = {Wagner, Michael and Bertero, Edoardo and Nickel, Alexander and Kohlhaas, Michael and Gibson, Gary E. and Heggermont, Ward and Heymans, Stephane and Maack, Christoph},
  title     = {Selective NADH communication from α-ketoglutarate dehydrogenase to mitochondrial transhydrogenase prevents reactive oxygen species formation under reducing conditions in the heart},
  series = {Basic Research in Cardiology},
  volume    = {115},
  journal   = {Basic Research in Cardiology},
  issn      = {0300-8428},
  doi       = {10.1007/s00395-020-0815-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234907},
  year      = {2020},
  abstract  = {In heart failure, a functional block of complex I of the respiratory chain provokes superoxide generation, which is transformed to H\(_2\)O\(_2\) by dismutation. The Krebs cycle produces NADH, which delivers electrons to complex I, and NADPH for H\(_2\)O\(_2\) elimination via isocitrate dehydrogenase and nicotinamide nucleotide transhydrogenase (NNT). At high NADH levels, α-ketoglutarate dehydrogenase (α-KGDH) is a major source of superoxide in skeletal muscle mitochondria with low NNT activity. Here, we analyzed how α-KGDH and NNT control H\(_2\)O\(_2\) emission in cardiac mitochondria. In cardiac mitochondria from NNT-competent BL/6N mice, H\(_2\)O\(_2\) emission is equally low with pyruvate/malate (P/M) or α-ketoglutarate (α-KG) as substrates. Complex I inhibition with rotenone increases H2O2 emission from P/M, but not α-KG respiring mitochondria, which is potentiated by depleting H\(_2\)O\(_2\)-eliminating capacity. Conversely, in NNT-deficient BL/6J mitochondria, H2O2 emission is higher with α-KG than with P/M as substrate, and further potentiated by complex I blockade. Prior depletion of H\(_2\)O\(_2\)-eliminating capacity increases H\(_2\)O\(_2\) emission from P/M, but not α-KG respiring mitochondria. In cardiac myocytes, downregulation of α-KGDH activity impaired dynamic mitochondrial redox adaptation during workload transitions, without increasing H\(_2\)O\(_2\) emission. In conclusion, NADH from α-KGDH selectively shuttles to NNT for NADPH formation rather than to complex I of the respiratory chain for ATP production. Therefore, α-KGDH plays a key role for H\(_2\)O\(_2\) elimination, but is not a relevant source of superoxide in heart. In heart failure, α-KGDH/NNT-dependent NADPH formation ameliorates oxidative stress imposed by complex I blockade. Downregulation of α-KGDH may, therefore, predispose to oxidative stress in heart failure.},
  language  = {en}
}
@phdthesis{Mohammadi2019,
  author    = {Mohammadi, Milad},
  title     = {Role of oxidized phospholipids in inflammatory pain},
  doi       = {10.25972/OPUS-19240},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-192402},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Introduction: During inflammation, reactive oxygen species (ROS) such as Hydrogen peroxide accumulate at the inflammation site and by oxidizing lipids, they produce metabolites such as 4-hydroxynonenal (4-HNE) and oxidized phospholipids (OxPLs). Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) are ligand gated ion channels that are expressed on nociceptors and their activation elicits pain. Hydrogen peroxide and 4-HNE are endogenous ligands for TRPA1 and their role in inflammatory pain conditions has been shown. OxPLs play a major pro-inflammatory role in many pathologies including atherosclerosis and multiple sclerosis. E06/T15 is a mouse IgM mAb that specifically binds oxidized phosphatidylcholine. D-4F is an apolipoprotein A-I mimetic peptide with a very high affinity for OxPLs and possess anti-inflammatory properties. E06 mAb and D-4F peptide protect against OxPLs-induced damage in atherosclerosis in vivo. Methods: To investigate the role of ROS and their metabolites in inflammatory pain, I utilized a combination of diverse and complex behavioral pain measurements and binding assays. I examined E06 mAb and D-4F as local treatment options for hypersensitivity evoked by endogenous and exogenous activators of TRPA1 and TRPV1 as well as in inflammatory and OxPL-induced pain models in vivo. 4-HNE, hydrogen peroxide as ROS source and mustard oil (AITC) were used to activate TRPA1, while capsaicin was used to activate TRPV1. Results: Intraplantar injection of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) into rats' hind paw elicited thermal and mechanical hypersensitivity. Genetic and pharmacological evidence in vivo confirmed the role of TRPA1 in OxPLs-induced hypersensitivity. OxPLs formation increased in complete Freund's adjuvant (CFA)-induced inflamed rats' paw. E06 mAb and D-4F prevented OxPAPC-induced mechanical and thermal hypersensitivity (hyperalgesia) as well as CFA-induced mechanical hypersensitivity. Also, all irritants induced thermal and mechanical hypersensitivity as well as affective-emotional responses and spontaneous nocifensive behaviors. E06 mAb blocked prolonged mechanical hypersensitivity by all but hydrogen peroxide. In parallel, D-4F prevented mechanical hypersensitivity induced by all irritants as well as thermal hypersensitivity induced by capsaicin and 4-HNE. In addition, competitive binding assays showed that all TRPA1/V1 agonists induced prolonged formation of OxPLs in the paw tissue explaining the anti-nociceptive properties of E06 mAb and D-4F. Finally, the potential of gait analysis as a readout for non-provoked pain behavioral measurements were examined. Conclusion and implications: OxPLs were characterized as novel targets in inflammatory pain. Treatment with the monoclonal antibody E06 or apolipoprotein A-I mimetic peptide D-4F are suggested as potential inflammatory pain medications. OxPLs' role in neuropathic pain is yet to be investigated.},
  language  = {en}
}
@phdthesis{Brandes2010,
  author    = {Brandes, Nicolas},
  title     = {Oxidative Thiol Modifications in Pro- and Eukaryotic Organisms},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-46542},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2010},
  abstract  = {Cystein spielt eine wichtige Rolle in der Biochemie vieler Proteine. Aufgrund der Redox-Eigenschaften und der hohen Reaktivit{\"a}t der freien Thiol-Gruppe sowie dessen F{\"a}higkeit Metallionen zu koordinieren, ist Cystein oft Bestandteil von katalytischen Zentren vieler Enzyme. Zudem lassen sich Cysteine durch reaktive Sauerstoff- und Stickstoffspezies leicht reversibel oxidativ modifizieren. In den letzten Jahren wurde gezeigt, dass Proteine redox-bedingte Thiol-Modifikationen nutzen, um Ver{\"a}nderungen ihrer Aktivit{\"a}t zu steuern. Diese redox-regulierten Proteine spielen eine zentrale Rolle in vielen physiologischen Prozessen. Das erste Ziel meiner Arbeit war die Identifizierung von Stickstoffmonoxid (NO)-sensitiven Proteinen in E. coli. Die redox-bedingten Funktions{\"a}nderungen solcher Proteine erkl{\"a}ren m{\"o}glicherweise die ver{\"a}nderte Physiologie von E. coli Zellen, die unter NO-Stress leiden. Um E. coli Proteine zu identifizieren, die unter Einwirkung von NO-Stress reversibel Thiol-modifiziert werden, wandte ich eine Kombination aus differentiellem Thiol-Trapping und 2D Gel-Elektrophorese an. Es wurden zehn Proteinen identifiziert, welche NO-sensitive Thiol-Gruppen enthalten. Genetische Studien ergaben, dass Modifikationen an AceF \& IlvC mitverantwortlich sind f{\"u}r die NO-induzierte Wachstumshemmung. Bemerkenswert ist es, dass die Mehrheit der identifizierten Proteine speziell nur gegen reaktive Stickstoffspezies empfindlich ist, welches an einem der identifizierten Stickstoffmonoxid-sensitiven Proteinen, der kleinen Untereinheit von Glutamate synthase, getestet wurde. In vivo und in vitro Aktivit{\"a}tsstudien zeigten, dass es zu einer schnellen Inaktivierung von Glutamate synthase nach NO-Behandlung kommt, das Protein aber resistent gegen{\"u}ber anderen Oxidationsmittel ist. Diese Resultate implizieren, dass reaktive Sauerstoff- und Stickstoffspezies unterschiedliche physiologische Vorg{\"a}nge in Bakterien beeinflussen. Das zweite Ziel meiner Arbeit war es, redox-sensitive Proteine in S. cerevisiae zu identifizieren und deren Redox-Zustand als in vivo Read-Out zu verwenden, um die Rolle von oxidativen Stress w{\"a}hrend des Alterungsprozess eukaryotischer Zellen zu analysieren. Zun{\"a}chst bestimmte ich in Hefezellen mit Hilfe von OxICAT, einer hochsensiblen quantitativen Methode, die Thiol-Trapping mit Massenspektrometrie verbindet, den exakten in vivo Thiol-Status von fast 300 Proteinen. Diese Proteine lassen sich in vier Gruppen einteilen: 1) Proteine, deren Cysteinreste resistent gegen Oxidation sind; 2) Proteine, in denen Cysteinmodifikationen strukturelle Aufgaben {\"u}bernehmen; 3) Proteine mit oxidationsempfindlichen Cysteinen, die bereits eine gewisse Oxidation in exponentiell wachsenden Hefezellen aufweisen; 4) Proteine, die reduziert sind, aber redox-sensitive Cysteinreste enthalten, die die Funktion der Proteine bei Vorhandensein von oxidativen Stress beeinflussen. Die Sensitivit{\"a}t dieser Proteine gegen{\"u}ber oxidativen Stress wurde durch Exposition subletaler Konzentrationen von H2O2 oder Superoxid auf Hefezellen nachgewiesen. Es wurde gezeigt, dass die wichtigsten zellul{\"a}ren Angriffspunkte von H2O2- und Superoxid-bedingtem Stress Proteine sind, die an Vorg{\"a}ngen der Translation, Glykolyse, des Citratzyklus und der Aminos{\"a}ure-Biosynthese beteiligt sind. Diese Zielproteine zeigen, dass Zellen f{\"u}r die Bek{\"a}mpfung von oxidativen Stress Metabolite schnell in Richtung des Pentosephosphatweges umleiten, um die Produktion des Reduktionsmittels NADPH sicherzustellen. Die hier pr{\"a}sentierten Ergebnisse belegen, dass die quantitative Bestimmung des Oxidationsstatus von Proteinen eine wertvolle Methode ist, um redox-sensitive Cysteinreste zu identifizieren. Die OxICAT Technologie wurde dann verwendet, um das genaue Ausmaß und die Entstehung von oxidativen Stress in chronologisch alternden S. cerevisiae Zellen zu bestimmen. F{\"u}r diese Bestimmung wurde der Oxidationsstatus von Proteinen in alternden Hefezellen als physiologischer Read-Out verwendet. Ich zeigte, dass die zellul{\"a}re Redox-Hom{\"o}ostase in chronologisch alternden Hefezellen global zusammenbricht, wobei es sich dabei um einen Prozess handelt, der dem Zelltod vorausgeht. Der Beginn dieses Zusammenbruchs scheint mit der Lebensdauer der Hefezellen zu korrelieren, da Kalorienrestriktion die Lebensdauer der Hefezellen erh{\"o}ht und den Zusammenbruch des Redox-Gleichgewichts verz{\"o}gert. Die Oxidation einer kleinen Anzahl an Proteinen (z.B. Thioredoxin reductase) geht dem Redox-Zusammenbruch deutlich voraus, was maßgeblich zum Verlust der Redox-Hom{\"o}ostase beitragen k{\"o}nnte. Diese Studien an alternden Hefezellen erweitern unser Verst{\"a}ndnis, wie sich Ver{\"a}nderungen in der Redox-Hom{\"o}ostase auf die Lebensdauer von Hefezellen auswirken. Zudem best{\"a}tigen die hier pr{\"a}sentierten Ergebnisse die Bedeutung von oxidativen Thiol-Modifikationen als eine der wichtigsten posttranslationalen Proteinmodifikationen in pro-und eukaryotischen Organismen},
  subject      = {Oxidativer Stress},
  language  = {en}
}
@article{SchwemmleinMaackBertero2022,
  author    = {Schwemmlein, Julia and Maack, Christoph and Bertero, Edoardo},
  title     = {Mitochondria as therapeutic targets in heart failure},
  series = {Current Heart Failure Reports},
  volume    = {19},
  journal   = {Current Heart Failure Reports},
  number    = {2},
  doi       = {10.1007/s11897-022-00539-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324015},
  pages     = {27-37},
  year      = {2022},
  abstract  = {Purpose of Review We review therapeutic approaches aimed at restoring function of the failing heart by targeting mitochondrial reactive oxygen species (ROS), ion handling, and substrate utilization for adenosine triphosphate (ATP) production. Recent Findings Mitochondria-targeted therapies have been tested in animal models of and humans with heart failure (HF). Cardiac benefits of sodium/glucose cotransporter 2 inhibitors might be partly explained by their effects on ion handling and metabolism of cardiac myocytes. Summary The large energy requirements of the heart are met by oxidative phosphorylation in mitochondria, which is tightly regulated by the turnover of ATP that fuels cardiac contraction and relaxation. In heart failure (HF), this mechano-energetic coupling is disrupted, leading to bioenergetic mismatch and production of ROS that drive the progression of cardiac dysfunction. Furthermore, HF is accompanied by changes in substrate uptake and oxidation that are considered detrimental for mitochondrial oxidative metabolism and negatively affect cardiac efficiency. Mitochondria lie at the crossroads of metabolic and energetic dysfunction in HF and represent ideal therapeutic targets.},
  language  = {en}
}
@article{DudekMaack2022,
  author    = {Dudek, Jan and Maack, Christoph},
  title     = {Mechano-energetic aspects of Barth syndrome},
  series = {Journal of Inherited Metabolic Disease},
  volume    = {45},
  journal   = {Journal of Inherited Metabolic Disease},
  number    = {1},
  doi       = {10.1002/jimd.12427},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257512},
  pages     = {82-98},
  year      = {2022},
  abstract  = {Energy-demanding organs like the heart are strongly dependent on oxidative phosphorylation in mitochondria. Oxidative phosphorylation is governed by the respiratory chain located in the inner mitochondrial membrane. The inner mitochondrial membrane is the only cellular membrane with significant amounts of the phospholipid cardiolipin, and cardiolipin was found to directly interact with a number of essential protein complexes, including respiratory chain complexes I to V. An inherited defect in the biogenesis of cardiolipin causes Barth syndrome, which is associated with cardiomyopathy, skeletal myopathy, neutropenia and growth retardation. Energy conversion is dependent on reducing equivalents, which are replenished by oxidative metabolism in the Krebs cycle. Cardiolipin deficiency in Barth syndrome also affects Krebs cycle activity, metabolite transport and mitochondrial morphology. During excitation-contraction coupling, calcium (Ca\(^{2+}\)) released from the sarcoplasmic reticulum drives sarcomeric contraction. At the same time, Ca\(^{2+}\) influx into mitochondria drives the activation of Krebs cycle dehydrogenases and the regeneration of reducing equivalents. Reducing equivalents are essential not only for energy conversion, but also for maintaining a redox buffer, which is required to detoxify reactive oxygen species (ROS). Defects in CL may also affect Ca\(^{2+}\) uptake into mitochondria and thereby hamper energy supply and demand matching, but also detoxification of ROS. Here, we review the impact of cardiolipin deficiency on mitochondrial function in Barth syndrome and discuss potential therapeutic strategies.},
  language  = {en}
}
@article{Meierjohann2015,
  author    = {Meierjohann, Svenja},
  title     = {Hypoxia independent drivers of melanoma angiogenesis},
  series = {Frontiers in Oncology},
  volume    = {5},
  journal   = {Frontiers in Oncology},
  number    = {120},
  doi       = {10.3389/fonc.2015.00102},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125586},
  year      = {2015},
  abstract  = {Tumor angiogenesis is a process which is traditionally regarded as the tumor's response to low nutrient supply occurring under hypoxic conditions. However, hypoxia is not a pre-requisite for angiogenesis. The fact that even single tumor cells or small tumor cell aggregates are capable of attracting blood vessels reveals the early metastatic capability of tumor cells. This review sheds light on the hypoxia-independent mechanisms of tumor angiogenesis in melanoma.},
  language  = {en}
}
@article{OckermannLizioHansmann2022,
  author    = {Ockermann, Philipp and Lizio, Rosario and Hansmann, Jan},
  title     = {Healthberry 865\(^®\) and a subset of its single anthocyanins attenuate oxidative stress in human endothelial in vitro models},
  series = {Nutrients},
  volume    = {14},
  journal   = {Nutrients},
  number    = {14},
  issn      = {2072-6643},
  doi       = {10.3390/nu14142917},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281887},
  year      = {2022},
  abstract  = {Oxidative stress and inflammation play a pivotal role in the development of cardiovascular diseases, an ever-growing worldwide problem. As a non-pharmacological approach, diet, especially a flavonoid-rich diet, showed promising results in the reduction of cardiovascular diseases and alleviation of their symptoms. In this study, in vitro systems based on human microvascular endothelial cells (hmvEC) and human umbilical cord endothelial cells (HUVEC) were established to determine the effect of Healthberry 865\(^®\) (HB) and ten of its relating single anthocyanins on oxidative stress. Furthermore, five metabolites were used in order to examine the effect of anthocyanin's most common breakdown molecules. The results showed an effect of HB in both models after 24 h, as well as most of its single anthocyanins. Cyanidin-rutinoside, peonidin-galactoside, and petunidin-glucoside had a model-specific effect. For the metabolites, phloroglucinaldeyhde (PGA) showed an effect in both models, while vanillic acid (VA) only had an effect in HUVEC. When combined, a combination of several anthocyanins did not have a cumulative effect, except for combining glucosides in hmvEC. The combination of PGA and VA even revealed an inhibitive behavior. Overall, the study demonstrates the antioxidative effect of HB and several of its single anthocyanins and metabolites, which are partially model specific, and coincides with animal studies.},
  language  = {en}
}
@phdthesis{Czisch2004,
  author    = {Czisch, Michael},
  title     = {Die Rolle von Bcl-2 bei der UV- und TRAIL-induzierten Keratinozytenapoptose},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-10903},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2004},
  abstract  = {In Keratinozyten wird sowohl durch UVB als auch durch PUVA-Bestrahlung Apoptose induziert. Wir untersuchten die in Keratinozyten durch UVB, PUVA, UVA und Todesliganden wie TRAIL ausgel{\"o}sten Apoptosewege n{\"a}her. UVB und PUVA, nicht aber UVA-Bestrahlung l{\"o}sen in vitro Keratinozytenapoptose aus. 2-4 h nach UVB beobachteten wir die Aktivierung von Caspasen. Nach PUVA setzt die Aktivierung von Caspasen wesentlich sp{\"a}ter ein, n{\"a}mlich erst 12 h nach Bestrahlung. Passend dazu, ist ein Verlust des mitochondrialen Transmembranpotentials 6-8 h nach UVB und 12-14 h nach PUVA detektierbar. Die {\"U}berexpression des Proteins Bcl-2 verhindert den Verlust des mitochondrialen Transmembranpotentials und die Caspase-Aktivierung nach UVB, und vermittelt auch einen klonogen Schutz, unabh{\"a}ngig von der Bildung reaktiver Sauerstoffradikale. Im Gegensatz dazu verz{\"o}gert es den Verlust des Transmembranpotentials und die Caspase-Aktivierung nach PUVA nur und verhindert sie nicht. PUVA-bestrahlte Zellen k{\"o}nnen sich nicht weiter teilen, sind also durch Bcl-2 nicht klonogen gesch{\"u}tzt.},
  language  = {de}
}
@article{OehlerKlokaMohammadietal.2020,
  author    = {Oehler, Beatrice and Kloka, Jan and Mohammadi, Milad and Ben-Kraiem, Adel and Rittner, Heike L.},
  title     = {D-4F, an ApoA-I mimetic peptide ameliorating TRPA1-mediated nocifensive behaviour in a model of neurogenic inflammation},
  series = {Molecular Pain},
  volume    = {16},
  journal   = {Molecular Pain},
  doi       = {10.1177/1744806920903848},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236061},
  pages     = {1-11},
  year      = {2020},
  abstract  = {Background High doses of capsaicin are recommended for the treatment of neuropathic pain. However, low doses evoke mechanical hypersensitivity. Activation of the capsaicin chemosensor transient receptor potential vanilloid 1 (TRPV1) induces neurogenic inflammation. In addition to the release of pro-inflammatory mediators, reactive oxygen species are produced. These highly reactive molecules generate oxidised phospholipids and 4-hydroxynonenal (4-HNE) which then directly activate TRP ankyrin 1 (TRPA1). The apolipoprotein A-I mimetic peptide D-4F neutralises oxidised phospholipids. Here, we asked whether D-4F ameliorates neurogenic hypersensitivity in rodents by targeting reactive oxygen species and 4-HNE in the capsaicin-evoked pain model. Results Co-application of D-4F ameliorated capsaicin-induced mechanical hypersensitivity and allodynia as well as persistent heat hypersensitivity measured by Randell-Selitto, von Frey and Hargreaves test, respectively. In addition, mechanical hypersensitivity was blocked after co-injection of D-4F with the reactive oxygen species analogue H2O2 or 4-HNE. In vitro studies on dorsal root ganglion neurons and stably transfected cell lines revealed a TRPA1-dependent inhibition of the calcium influx when agonists were pre-incubated with D-4F. The capsaicin-induced calcium influx in TRPV1-expressing cell lines and dorsal root ganglion neurons sustained in the presence of D-4F. Conclusions D-4F is a promising compound to ameliorate TRPA1-dependent hypersensitivity during neurogenic inflammation.},
  language  = {en}
}
@article{OttoHahlbrockEichetal.2016,
  author    = {Otto, Christoph and Hahlbrock, Theresa and Eich, Kilian and Karaaslan, Ferdi and J{\"u}rgens, Constantin and Germer, Christoph-Thomas and Wiegering, Armin and K{\"a}mmerer, Ulrike},
  title     = {Antiproliferative and antimetabolic effects behind the anticancer property of fermented wheat germ extract},
  series = {BMC Complementary and Alternative Medicine},
  volume    = {16},
  journal   = {BMC Complementary and Alternative Medicine},
  number    = {160},
  doi       = {10.1186/s12906-016-1138-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146013},
  year      = {2016},
  abstract  = {Background Fermented wheat germ extract (FWGE) sold under the trade name Avemar exhibits anticancer activity in vitro and in vivo. Its mechanisms of action are divided into antiproliferative and antimetabolic effects. Its influcence on cancer cell metabolism needs further investigation. One objective of this study, therefore, was to further elucidate the antimetabolic action of FWGE. The anticancer compound 2,6-dimethoxy-1,4-benzoquinone (DMBQ) is the major bioactive compound in FWGE and is probably responsible for its anticancer activity. The second objective of this study was to compare the antiproliferative properties in vitro of FWGE and the DMBQ compound. Methods The IC\(_{50}\) values of FWGE were determined for nine human cancer cell lines after 24 h of culture. The DMBQ compound was used at a concentration of 24 μmol/l, which is equal to the molar concentration of DMBQ in FWGE. Cell viability, cell cycle, cellular redox state, glucose consumption, lactic acid production, cellular ATP levels, and the NADH/NAD\(^+\) ratio were measured. Results The mean IC\(_{50}\) value of FWGE for the nine human cancer cell lines tested was 10 mg/ml. Both FWGE (10 mg/ml) and the DMBQ compound (24 μmol/l) induced massive cell damage within 24 h after starting treatment, with changes in the cellular redox state secondary to formation of intracellular reactive oxygen species. Unlike the DMBQ compound, which was only cytotoxic, FWGE exhibited cytostatic and growth delay effects in addition to cytotoxicity. Both cytostatic and growth delay effects were linked to impaired glucose utilization which influenced the cell cycle, cellular ATP levels, and the NADH/NAD\(^+\) ratio. The growth delay effect in response to FWGE treatment led to induction of autophagy. Conclusions FWGE and the DMBQ compound both induced oxidative stress-promoted cytotoxicity. In addition, FWGE exhibited cytostatic and growth delay effects associated with impaired glucose utilization which led to autophagy, a possible previously unknown mechanism behind the influence of FWGE on cancer cell metabolism.},
  language  = {en}
}
@article{KleefeldtBoemmelBroedeetal.2019,
  author    = {Kleefeldt, Florian and B{\"o}mmel, Heike and Broede, Britta and Thomsen, Michael and Pfeiffer, Verena and W{\"o}rsd{\"o}rfer, Philipp and Karnati, Srikanth and Wagner, Nicole and Rueckschloss, Uwe and Erg{\"u}n, S{\"u}leyman},
  title     = {Aging-related carcinoembryonic antigen-related cell adhesion molecule 1 signaling promotes vascular dysfunction},
  series = {Aging Cell},
  volume    = {2019},
  journal   = {Aging Cell},
  number    = {18},
  doi       = {10.1111/acel.13025},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201231},
  pages     = {e13025},
  year      = {2019},
  abstract  = {Aging is an independent risk factor for cardiovascular diseases and therefore of particular interest for the prevention of cardiovascular events. However, the mechanisms underlying vascular aging are not well understood. Since carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is crucially involved in vascular homeostasis, we sought to identify the role of CEACAM1 in vascular aging. Using human internal thoracic artery and murine aorta, we show that CEACAM1 is upregulated in the course of vascular aging. Further analyses demonstrated that TNF-α is CEACAM1-dependently upregulated in the aging vasculature. Vice versa, TNF-α induces CEACAM1 expression. This results in a feed-forward loop in the aging vasculature that maintains a chronic pro-inflammatory milieu. Furthermore, we demonstrate that age-associated vascular alterations, that is, increased oxidative stress and vascular fibrosis, due to increased medial collagen deposition crucially depend on the presence of CEACAM1. Additionally, age-dependent upregulation of vascular CEACAM1 expression contributes to endothelial barrier impairment, putatively via increased VEGF/VEGFR-2 signaling. Consequently, aging-related upregulation of vascular CEACAM1 expression results in endothelial dysfunction that may promote atherosclerotic plaque formation in the presence of additional risk factors. Our data suggest that CEACAM1 might represent an attractive target in order to delay physiological aging and therefore the transition to vascular disorders such as atherosclerosis.},
  language  = {en}
}