BEGIN:VCALENDAR VERSION:2.0 PRODID:www.dresden-science-calendar.de METHOD:PUBLISH CALSCALE:GREGORIAN X-MICROSOFT-CALSCALE:GREGORIAN X-WR-TIMEZONE:Europe/Berlin BEGIN:VTIMEZONE TZID:Europe/Berlin X-LIC-LOCATION:Europe/Berlin BEGIN:DAYLIGHT TZNAME:CEST TZOFFSETFROM:+0100 TZOFFSETTO:+0200 DTSTART:19810329T030000 RRULE:FREQ=YEARLY;INTERVAL=1;BYMONTH=3;BYDAY=-1SU END:DAYLIGHT BEGIN:STANDARD TZNAME:CET TZOFFSETFROM:+0200 TZOFFSETTO:+0100 DTSTART:19961027T030000 RRULE:FREQ=YEARLY;INTERVAL=1;BYMONTH=10;BYDAY=-1SU END:STANDARD END:VTIMEZONE BEGIN:VEVENT UID:DSC-21344 DTSTART;TZID=Europe/Berlin:20241018T110000 SEQUENCE:1729229941 TRANSP:OPAQUE DTEND;TZID=Europe/Berlin:20241018T120000 URL:https://www.dresden-science-calendar.de/calendar/de/detail/21344 LOCATION:MPI-CBG\, Pfotenhauerstraße 10801307 Dresden SUMMARY:Pedrero: Keap1 deletion rescues cell death associated with Gpx4 los s in hepatocytes during acute liver injury CLASS:PUBLIC DESCRIPTION:Speaker: Leticia Colyn Pedrero\nInstitute of Speaker: Departmen t of Internal Medicine III\, University Hospital RWTH Aachen\, Germany\nTo pics:\n\n Location:\n Name: MPI-CBG (MPI-CBG: Galleria)\n Street: Pfoten hauerstraße 108\n City: 01307 Dresden\n Phone: +49 351 210-0\n Fax: +4 9 351 210-2000\nDescription: Acute liver failure (ALF) is a life-threateni ng condition with limited treatment options beyond liver transplantation i n non-acetaminophen cases. The extensive loss of liver function results fr om severe hepatocyte death\, where elevated reactive oxygen species (ROS) play a significant role. Nuclear factor erythroid-2 like 2 (Nrf2) is cruci al in ROS defense by regulating genes such as glutathione peroxidase 4 (GP X4)\, which prevents lipid peroxidation (LPO). GPX4 is involved in several regulated cell processes\, including apoptosis and ferroptosis. GPX4 expr ession was measured in liver samples from healthy individuals\, ALF\, and acute-on-chronic liver failure (ACLF) patients. To investigate GPX4's role \, mice with hepatocyte-specific deletion of Gpx4 (Gpx4&\;#916\;hepa) a nd both Gpx4 and the Nrf2 repressor\, Keap1\, (Gpx4&\;#916\;hepaKeap1&a mp\;#916\;hepa) were generated. ALF was induced in mice using a carbon tet rachloride (CCl4) and a bile duct ligation (BDL) cholestasis model\, each lasting 48 hours. ALF patients exhibited reduced GPX4 levels compared to h ealthy individuals and ACLF patients\, consistent with observations in CCl 4-treated wild- type mice. ALF-induced Gpx4&\;#916\;hepa mice exhibited increased hepatocyte death and liver dysfunction upon CCl4 treatment\, wi th increased apoptosis despite no changes in LPO markers. Activation of Nr f2 in Gpx4&\;#916\;hepaKeap1&\;#916\;hepamice reversed CCl4-induced damage\, reducing necrosis and apoptosis markers while inducing anti-apopt otic BCL2. Our results demonstrate that Gpx4 plays a critical role in ALF as its absence leads to hepatocyte apoptosis. Activating Keap1-dependent p athways targeting antioxidant defense system and upregulating BCL2 provide s substantial protection against ALF in mice lacking Gpx4 in hepatocytes. Our findings suggest that the Keap1-Nrf2 axis is a promising therapeutic t arget in ALF. DTSTAMP:20260730T102655Z CREATED:20241010T054117Z LAST-MODIFIED:20241018T053901Z END:VEVENT END:VCALENDAR