Beneficial Role of ROS in Cell Survival: Moderate Increases in H<sub>2</sub>O<sub>2</sub> 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 RO...
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| Format: | Article |
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MDPI AG
2019-10-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/8/10/434 |
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| author | Izak Patrik Miller Ivan Pavlović Borut Poljšak Dušan Šuput Irina Milisav |
| author_facet | Izak Patrik Miller Ivan Pavlović Borut Poljšak Dušan Šuput Irina Milisav |
| author_sort | Izak Patrik Miller |
| collection | DOAJ |
| description | 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<sub>2</sub>O<sub>2</sub> and concomitant upregulation of antioxidative enzymes triggered by hepatocyte isolation; the H<sub>2</sub>O<sub>2</sub> 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<sub>2</sub>O<sub>2</sub> 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<sub>2</sub>O<sub>2</sub> production, as decreased production of H<sub>2</sub>O<sub>2</sub> 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. |
| first_indexed | 2024-03-12T11:00:41Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-12T11:00:41Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj.art-8ee594b7e66f465c9ec2c6b0d6958ddb2023-09-02T05:48:46ZengMDPI AGAntioxidants2076-39212019-10-0181043410.3390/antiox8100434antiox8100434Beneficial Role of ROS in Cell Survival: Moderate Increases in H<sub>2</sub>O<sub>2</sub> Production Induced by Hepatocyte Isolation Mediate Stress Adaptation and Enhanced SurvivalIzak Patrik Miller0Ivan Pavlović1Borut Poljšak2Dušan Šuput3Irina Milisav4Faculty of Medicine, Institute of Pathophysiology, University of Ljubljana, Zaloska 4, SI-1000 Ljubljana, SloveniaLaboratory of Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Mike Petrovica Alasa 12-14, P.O. Box 522, 11001 Belgrade, SerbiaLaboratory of Oxidative Stress Research, Faculty of Health Sciences, University of Ljubljana, Zdravstvena pot 5, SI-1000 Ljubljana, SloveniaFaculty of Medicine, Institute of Pathophysiology, University of Ljubljana, Zaloska 4, SI-1000 Ljubljana, SloveniaFaculty of Medicine, Institute of Pathophysiology, University of Ljubljana, Zaloska 4, SI-1000 Ljubljana, SloveniaHigh 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<sub>2</sub>O<sub>2</sub> and concomitant upregulation of antioxidative enzymes triggered by hepatocyte isolation; the H<sub>2</sub>O<sub>2</sub> 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<sub>2</sub>O<sub>2</sub> 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<sub>2</sub>O<sub>2</sub> production, as decreased production of H<sub>2</sub>O<sub>2</sub> 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.https://www.mdpi.com/2076-3921/8/10/434hydrogen peroxidemitochondriaredox regulationcaspase-9apoptosis |
| spellingShingle | Izak Patrik Miller Ivan Pavlović Borut Poljšak Dušan Šuput Irina Milisav Beneficial Role of ROS in Cell Survival: Moderate Increases in H<sub>2</sub>O<sub>2</sub> Production Induced by Hepatocyte Isolation Mediate Stress Adaptation and Enhanced Survival Antioxidants hydrogen peroxide mitochondria redox regulation caspase-9 apoptosis |
| title | Beneficial Role of ROS in Cell Survival: Moderate Increases in H<sub>2</sub>O<sub>2</sub> Production Induced by Hepatocyte Isolation Mediate Stress Adaptation and Enhanced Survival |
| title_full | Beneficial Role of ROS in Cell Survival: Moderate Increases in H<sub>2</sub>O<sub>2</sub> Production Induced by Hepatocyte Isolation Mediate Stress Adaptation and Enhanced Survival |
| title_fullStr | Beneficial Role of ROS in Cell Survival: Moderate Increases in H<sub>2</sub>O<sub>2</sub> Production Induced by Hepatocyte Isolation Mediate Stress Adaptation and Enhanced Survival |
| title_full_unstemmed | Beneficial Role of ROS in Cell Survival: Moderate Increases in H<sub>2</sub>O<sub>2</sub> Production Induced by Hepatocyte Isolation Mediate Stress Adaptation and Enhanced Survival |
| title_short | Beneficial Role of ROS in Cell Survival: Moderate Increases in H<sub>2</sub>O<sub>2</sub> Production Induced by Hepatocyte Isolation Mediate Stress Adaptation and Enhanced Survival |
| title_sort | beneficial role of ros in cell survival moderate increases in h sub 2 sub o sub 2 sub production induced by hepatocyte isolation mediate stress adaptation and enhanced survival |
| topic | hydrogen peroxide mitochondria redox regulation caspase-9 apoptosis |
| url | https://www.mdpi.com/2076-3921/8/10/434 |
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