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 (author), Pavlović, Ivan (author), Poljšak, Borut (author), Šuput, Dušan (author), Milisav, Irina (author)

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.

• Language: English
• Keywords: hydrogen peroxide, mitochondria, redox regulation, caspase-9, apoptosis
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine; ZF - Faculty of Health Sciences
• Publication status: Published
• Publication version: Version of Record
• Year: 2019
• Number of pages: 14 str.
• Numbering: Vol. 8, iss. 10, art. 434
• PID: 20.500.12556/RUL-126358
• UDC: 616-092
• ISSN on article: 2076-3921
• DOI: 10.3390/antiox8100434
• COBISS.SI-ID: 34522073
• Publication date in RUL: 18.04.2021

Record is a part of a journal

• Title: Antioxidants
• Shortened title: Antioxidants
• Publisher: MDPI
• ISSN: 2076-3921
• COBISS.SI-ID: 522976025

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.10.2019

Secondary language

• Language: Slovenian
• Keywords: vodikov peroksid, mitohondrije, redoks regulacija

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0019
• Name: Aplikativna in bazična fiziologija in patofiziologija v medicini

• Funder: EC - European Commission
• Funding programme: H2020
• Project number: 721236
• Name: Training European Network: Metabolic Dysfunctions associated with Pharmacological Treatment of Schizophrenia
• Acronym: TREATMENT