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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...

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Autores principales: Miller, Izak Patrik, Pavlović, Ivan, Poljšak, Borut, Šuput, Dušan, Milisav, Irina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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