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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826461/ https://www.ncbi.nlm.nih.gov/pubmed/31581418 http://dx.doi.org/10.3390/antiox8100434 |
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author | Miller, Izak Patrik Pavlović, Ivan Poljšak, Borut Šuput, Dušan Milisav, Irina |
author_facet | Miller, Izak Patrik Pavlović, Ivan Poljšak, Borut Šuput, Dušan Milisav, Irina |
author_sort | Miller, Izak Patrik |
collection | PubMed |
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(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. |
format | Online Article Text |
id | pubmed-6826461 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68264612019-11-18 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 Miller, Izak Patrik Pavlović, Ivan Poljšak, Borut Šuput, Dušan Milisav, Irina Antioxidants (Basel) Article 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. MDPI 2019-10-01 /pmc/articles/PMC6826461/ /pubmed/31581418 http://dx.doi.org/10.3390/antiox8100434 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Miller, Izak Patrik Pavlović, Ivan Poljšak, Borut Šuput, Dušan Milisav, Irina 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826461/ https://www.ncbi.nlm.nih.gov/pubmed/31581418 http://dx.doi.org/10.3390/antiox8100434 |
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