TY  - JOUR
A1  - Bankoglu, Ezgi Eyluel
A1  - Tschopp, Oliver
A1  - Schmitt, Johannes
A1  - Burkard, Philipp
A1  - Jahn, Daniel
A1  - Geier, Andreas
A1  - Stopper, Helga
T1  - Role of PTEN in Oxidative Stress and DNA Damage in the Liver of Whole-Body Pten Haplodeficient Mice
JF  - PLoS One
N2  - Type 2 diabetes (T2DM) and obesity are frequently associated with non-alcoholic fatty liver disease (NAFLD) and with an elevated cancer incidence. The molecular mechanisms of carcinogenesis in this context are only partially understood. High blood insulin levels are typical in early T2DM and excessive insulin can cause elevated reactive oxygen species (ROS) production and genomic instability. ROS are important for various cellular functions in signaling and host defense. However, elevated ROS formation is thought to be involved in cancer induction. In the molecular events from insulin receptor binding to genomic damage, some signaling steps have been identified, pointing at the PI3K/AKT pathway. For further elucidation Phosphatase and Tensin homolog (Pten), a tumour suppressor phosphatase that plays a role in insulin signaling by negative regulation of PI3K/AKT and its downstream targets, was investigated here. Dihydroethidium (DHE) staining was used to detect ROS formation in immortalized human hepatocytes. Comet assay and micronucleus test were performed to investigate genomic damage in vitro. In liver samples, DHE staining and western blot detection of HSP70 and HO-1 were performed to evaluate oxidative stress response. DNA double strand breaks (DSBs) were detected by immunohistostaining. Inhibition of PTEN with the pharmacologic inhibitor VO-OHpic resulted in increased ROS production and genomic damage in a liver cell line. Knockdown of Pten in a mouse model yielded increased oxidative stress levels, detected by ROS levels and expression of the two stress-proteins HSP70 and HO-1 and elevated genomic damage in the liver, which was significant in mice fed with a high fat diet. We conclude that PTEN is involved in oxidative stress and genomic damage induction in vitro and that this may also explain the in vivo observations. This further supports the hypothesis that the PI3K/AKT pathway is responsible for damaging effects of high levels of insulin.
KW  - insulin
KW  - mouse models DNA damage
KW  - oxidative stress
KW  - mammalian genomics
KW  - fatty liver
KW  - micronuclei
KW  - insulin signaling
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146970
VL  - 11
IS  - 11
ER  - 
TY  - JOUR
A1  - Taha, Muhamed-Kheir
A1  - Claus, Heike
A1  - Lappann, Martin
A1  - Veyrier, Frédéric J.
A1  - Otto, Andreas
A1  - Becher, Dörte
A1  - Deghmane, Ala-Eddine
A1  - Frosch, Matthias
A1  - Hellenbrand, Wiebke
A1  - Hong, Eva
A1  - du Châtelet, Isabelle Parent
A1  - Prior, Karola
A1  - Harmsen, Dag
A1  - Vogel, Ulrich
T1  - Evolutionary Events Associated with an Outbreak of Meningococcal Disease in Men Who Have Sex with Men
JF  - PLoS ONE
N2  - Meningococci spread via respiratory droplets, whereas the closely related gonococci are transmitted sexually. Several outbreaks of invasive meningococcal disease have been reported in Europe and the United States among men who have sex with men (MSM). We recently identified an outbreak of serogroup C meningococcal disease among MSM in Germany and France. In this study, genomic and proteomic techniques were used to analyze the outbreak isolates. In addition, genetically identical urethritis isolates were recovered from France and Germany and included in the analysis. Genome sequencing revealed that the isolates from the outbreak among MSM and from urethritis cases belonged to a clade within clonal complex 11. Proteome analysis showed they expressed nitrite reductase, enabling anaerobic growth as previously described for gonococci. Invasive isolates from MSM, but not urethritis isolates, further expressed functional human factor H binding protein associated with enhanced survival in a newly developed transgenic mouse model expressing human factor H, a complement regulatory protein. In conclusion, our data suggest that urethritis and outbreak isolates followed a joint adaptation route including adaption to the urogenital tract.
KW  - nitrites
KW  - genome sequencing
KW  - men who have sex with men
KW  - meningococcal disease
KW  - Neisseria meningitidis
KW  - Neisseria gonorrhoeae
KW  - mammalian genomics
KW  - mouse models
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-179870
VL  - 11
IS  - 5
ER  -