20.500.12556/RUL-126358 Beneficial role of ROS in cell survival moderate increases in H$_2$O$_2$ production induced by hepatocyte isolation mediate stress adaptation and enhanced survival High levels of reactive oxygen species (ROS) can lead to impairment of cell structure, biomolecules' loss of function and cell death and are associated with liver diseases. Cells that survive increased ROS often undergo malignant transformation. Many cancer cells tolerate high levels of ROS. Here we report a transiently increased production of H$_2$O$_2$ and concomitant upregulation of antioxidative enzymes triggered by hepatocyte isolation; the H$_2$O$_2$ levels revert in about two days in culture. Three-day survival rate of the isolated cells in the presence of 2.5-fold increase of H$_2$O$_2$ is almost 80%. Apoptosis activation through the mitochondrial pathway is meanwhile reduced by inhibition of caspase-9 triggering. This reduction depends on the amount of H$_2$O$_2$ production, as decreased production of H$_2$O$_2$ in the presence of an antioxidant results in increased apoptosis triggering. These stress adaptations do not influence urea production, which is unchanged throughout the normal and stress adapted phases. We conclude that hepatocytes' stress adaptation is mediated by increased ROS production. In this case, high ROS improve cell survival. hydrogen peroxide mitochondria redox regulation caspase-9 apoptosis vodikov peroksid mitohondrije redoks regulacija true false true Angleški jezik Slovenski jezik Članek v reviji 2021-04-18 20:16:24 2021-04-18 20:16:29 2022-09-05 03:54:54 0000-00-00 00:00:00 2019 0 0 14 str. iss. 10, art. 434 Vol. 8 2019 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-092 2076-3921 10.3390/antiox8100434 34522073 522976025 RAZ_Miller_Izak_Patrik_2019.pdf RAZ_Miller_Izak_Patrik_2019.pdf 1 175767748CCD5A4277974BE3A86D43D6 07aa6804762f58ce7c8ba0ebcd72dc98d5ea50727032117c4e76280fc25f3b02 7a7837ac-46c3-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=151055 RAZ_Miller_Izak_Patrik_2019.xlsx RAZ_Miller_Izak_Patrik_2019.xlsx Raziskovalni podatki, obravnavani v članku Research data underlying the article 1 F3E9A94473EB76A16A35E05422DFF60D 2fc08f0dc3b36b727434a2c066a335ab5906e26d25b8b5d160bb3a90b18a341a e4a4ebf8-a1bb-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=142276 https://www.mdpi.com/2076-3921/8/10/434 1 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=142274 Medicinska fakulteta Zdravstvena fakulteta 0 0 0