Cargando…
Human Relaxin-2 (Serelaxin) Attenuates Oxidative Stress in Cardiac Muscle Cells Exposed In Vitro to Hypoxia–Reoxygenation. Evidence for the Involvement of Reduced Glutathione Up-Regulation
Serelaxin (RLX) designates the pharmaceutical form of the human natural hormone relaxin-2 that has been shown to markedly reduce tissue and cell damage induced by hypoxia and reoxygenation (HR). The evidence that RLX exerts similar protective effects on different organs and cells at relatively low,...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555919/ https://www.ncbi.nlm.nih.gov/pubmed/32825567 http://dx.doi.org/10.3390/antiox9090774 |
_version_ | 1783594119216496640 |
---|---|
author | Nistri, Silvia Fiorillo, Claudia Becatti, Matteo Bani, Daniele |
author_facet | Nistri, Silvia Fiorillo, Claudia Becatti, Matteo Bani, Daniele |
author_sort | Nistri, Silvia |
collection | PubMed |
description | Serelaxin (RLX) designates the pharmaceutical form of the human natural hormone relaxin-2 that has been shown to markedly reduce tissue and cell damage induced by hypoxia and reoxygenation (HR). The evidence that RLX exerts similar protective effects on different organs and cells at relatively low, nanomolar concentrations suggests that it specifically targets a common pathogenic mechanism of HR-induced damage, namely oxidative stress. In this study we offer experimental evidence that RLX (17 nmol L-1), added to the medium of HR-exposed H9c2 rat cardiac muscle cells, significantly reduces cell oxidative damage, mitochondrial dysfunction and apoptosis. These effects appear to rely on the up-regulation of the cellular availability of reduced glutathione (GSH), a ubiquitous endogenous antioxidant metabolite. Conversely, superoxide dismutase activity was not influenced by RLX, which, however, was not endowed with chemical antioxidant properties. Taken together, these findings verify the major pharmacological role of RLX in the protection against HR-induced oxidative stress, and shed first light on its mechanisms of action. |
format | Online Article Text |
id | pubmed-7555919 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75559192020-10-19 Human Relaxin-2 (Serelaxin) Attenuates Oxidative Stress in Cardiac Muscle Cells Exposed In Vitro to Hypoxia–Reoxygenation. Evidence for the Involvement of Reduced Glutathione Up-Regulation Nistri, Silvia Fiorillo, Claudia Becatti, Matteo Bani, Daniele Antioxidants (Basel) Article Serelaxin (RLX) designates the pharmaceutical form of the human natural hormone relaxin-2 that has been shown to markedly reduce tissue and cell damage induced by hypoxia and reoxygenation (HR). The evidence that RLX exerts similar protective effects on different organs and cells at relatively low, nanomolar concentrations suggests that it specifically targets a common pathogenic mechanism of HR-induced damage, namely oxidative stress. In this study we offer experimental evidence that RLX (17 nmol L-1), added to the medium of HR-exposed H9c2 rat cardiac muscle cells, significantly reduces cell oxidative damage, mitochondrial dysfunction and apoptosis. These effects appear to rely on the up-regulation of the cellular availability of reduced glutathione (GSH), a ubiquitous endogenous antioxidant metabolite. Conversely, superoxide dismutase activity was not influenced by RLX, which, however, was not endowed with chemical antioxidant properties. Taken together, these findings verify the major pharmacological role of RLX in the protection against HR-induced oxidative stress, and shed first light on its mechanisms of action. MDPI 2020-08-21 /pmc/articles/PMC7555919/ /pubmed/32825567 http://dx.doi.org/10.3390/antiox9090774 Text en © 2020 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 Nistri, Silvia Fiorillo, Claudia Becatti, Matteo Bani, Daniele Human Relaxin-2 (Serelaxin) Attenuates Oxidative Stress in Cardiac Muscle Cells Exposed In Vitro to Hypoxia–Reoxygenation. Evidence for the Involvement of Reduced Glutathione Up-Regulation |
title | Human Relaxin-2 (Serelaxin) Attenuates Oxidative Stress in Cardiac Muscle Cells Exposed In Vitro to Hypoxia–Reoxygenation. Evidence for the Involvement of Reduced Glutathione Up-Regulation |
title_full | Human Relaxin-2 (Serelaxin) Attenuates Oxidative Stress in Cardiac Muscle Cells Exposed In Vitro to Hypoxia–Reoxygenation. Evidence for the Involvement of Reduced Glutathione Up-Regulation |
title_fullStr | Human Relaxin-2 (Serelaxin) Attenuates Oxidative Stress in Cardiac Muscle Cells Exposed In Vitro to Hypoxia–Reoxygenation. Evidence for the Involvement of Reduced Glutathione Up-Regulation |
title_full_unstemmed | Human Relaxin-2 (Serelaxin) Attenuates Oxidative Stress in Cardiac Muscle Cells Exposed In Vitro to Hypoxia–Reoxygenation. Evidence for the Involvement of Reduced Glutathione Up-Regulation |
title_short | Human Relaxin-2 (Serelaxin) Attenuates Oxidative Stress in Cardiac Muscle Cells Exposed In Vitro to Hypoxia–Reoxygenation. Evidence for the Involvement of Reduced Glutathione Up-Regulation |
title_sort | human relaxin-2 (serelaxin) attenuates oxidative stress in cardiac muscle cells exposed in vitro to hypoxia–reoxygenation. evidence for the involvement of reduced glutathione up-regulation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555919/ https://www.ncbi.nlm.nih.gov/pubmed/32825567 http://dx.doi.org/10.3390/antiox9090774 |
work_keys_str_mv | AT nistrisilvia humanrelaxin2serelaxinattenuatesoxidativestressincardiacmusclecellsexposedinvitrotohypoxiareoxygenationevidencefortheinvolvementofreducedglutathioneupregulation AT fiorilloclaudia humanrelaxin2serelaxinattenuatesoxidativestressincardiacmusclecellsexposedinvitrotohypoxiareoxygenationevidencefortheinvolvementofreducedglutathioneupregulation AT becattimatteo humanrelaxin2serelaxinattenuatesoxidativestressincardiacmusclecellsexposedinvitrotohypoxiareoxygenationevidencefortheinvolvementofreducedglutathioneupregulation AT banidaniele humanrelaxin2serelaxinattenuatesoxidativestressincardiacmusclecellsexposedinvitrotohypoxiareoxygenationevidencefortheinvolvementofreducedglutathioneupregulation |