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Beneficial Role of ROS in Cell Survival: Moderate Increases in H2O2 Production Induced by Hepatocyte Isolation Mediate Stress Adaptation and Enhanced Survival
Izak Patrik Miller 
1
Faculty of Medicine, Institute of Pathophysiology, University of Ljubljana, Zaloska 4, SI-1000 Ljubljana, Slovenia
2
Laboratory of Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Mike Petrovica Alasa 12-14, P.O. Box 522, 11001 Belgrade, Serbia
3
Laboratory of Oxidative Stress Research, Faculty of Health Sciences, University of Ljubljana, Zdravstvena pot 5, SI-1000 Ljubljana, Slovenia
*
Author to whom correspondence should be addressed.
Antioxidants 2019, 8(10), 434; https://doi.org/10.3390/antiox8100434
Received: 28 June 2019 / Revised: 7 September 2019 / Accepted: 17 September 2019 / Published: 1 October 2019
(This article belongs to the Special Issue Oxidative stress and Applied Biology)
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 H2O2 and concomitant upregulation of antioxidative enzymes triggered by hepatocyte isolation; the H2O2 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 H2O2 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 H2O2 production, as decreased production of H2O2 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.
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Keywords:
hydrogen peroxide; mitochondria; redox regulation; caspase-9; apoptosis
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MDPI and ACS Style
Miller, I.P.; Pavlović, I.; Poljšak, B.; Šuput, D.; Milisav, I. Beneficial Role of ROS in Cell Survival: Moderate Increases in H2O2 Production Induced by Hepatocyte Isolation Mediate Stress Adaptation and Enhanced Survival. Antioxidants 2019, 8, 434.
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