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

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.

• Jezik: Angleški jezik
• Ključne besede: hydrogen peroxide, mitochondria, redox regulation, caspase-9, apoptosis
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta ; ZF - Zdravstvena fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2019
• Št. strani: 14 str.
• Številčenje: Vol. 8, iss. 10, art. 434
• PID: 20.500.12556/RUL-126358
• UDK: 616-092
• ISSN pri članku: 2076-3921
• DOI: 10.3390/antiox8100434
• COBISS.SI-ID: 34522073
• Datum objave v RUL: 18.04.2021

Gradivo je del revije

• Naslov: Antioxidants
• Skrajšan naslov: Antioxidants
• Založnik: MDPI
• ISSN: 2076-3921
• COBISS.SI-ID: 522976025

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 01.10.2019

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: vodikov peroksid, mitohondrije, redoks regulacija

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P3-0019
• Naslov: Aplikativna in bazična fiziologija in patofiziologija v medicini

• Financer: EC - European Commission
• Program financ.: H2020
• Številka projekta: 721236
• Naslov: Training European Network: Metabolic Dysfunctions associated with Pharmacological Treatment of Schizophrenia
• Akronim: TREATMENT