Diazoxide Needs Mitochondrial Connexin43 to Exert Its Cytoprotective Effect in a Cellular Model of CoCl<sub>2</sub>-Induced Hypoxia

Hypoxia is the leading cause of death in cardiomyocytes. Cells respond to oxygen deprivation by activating cytoprotective programs, such as mitochondrial connexin43 (mCx43) overexpression and the opening of mitochondrial K<sub>ATP</sub> channels, aimed to reduce mitochondrial dysfunction...

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Autores principales:	Michela Pecoraro, Stefania Marzocco, Ada Popolo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mCx43 K<sub>ATP</sub> channels diazoxide chemical hypoxia Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/6340248dda6749b58ad770d5bd502cd4
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spelling	oai:doaj.org-article:6340248dda6749b58ad770d5bd502cd42021-11-11T17:04:38ZDiazoxide Needs Mitochondrial Connexin43 to Exert Its Cytoprotective Effect in a Cellular Model of CoCl<sub>2</sub>-Induced Hypoxia10.3390/ijms2221115991422-00671661-6596https://doaj.org/article/6340248dda6749b58ad770d5bd502cd42021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11599https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Hypoxia is the leading cause of death in cardiomyocytes. Cells respond to oxygen deprivation by activating cytoprotective programs, such as mitochondrial connexin43 (mCx43) overexpression and the opening of mitochondrial K<sub>ATP</sub> channels, aimed to reduce mitochondrial dysfunction. In this study we used an in vitro model of CoCl<sub>2</sub>-induced hypoxia to demonstrate that mCx43 and K<sub>ATP</sub> channels cooperate to induce cytoprotection. CoCl<sub>2</sub> administration induces apoptosis in H9c2 cells by increasing mitochondrial ROS production, intracellular and mitochondrial calcium overload and by inducing mitochondrial membrane depolarization. Diazoxide, an opener of K<sub>ATP</sub> channels, reduces all these deleterious effects of CoCl<sub>2</sub> only in the presence of mCx43. In fact, our results demonstrate that in the presence of radicicol, an inhibitor of Cx43 translocation to mitochondria, the cytoprotective effects of diazoxide disappear. In conclusion, these data confirm that there exists a close functional link between mCx43 and K<sub>ATP</sub> channels.Michela PecoraroStefania MarzoccoAda PopoloMDPI AGarticlemCx43K<sub>ATP</sub> channelsdiazoxidechemical hypoxiaBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11599, p 11599 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mCx43 K<sub>ATP</sub> channels diazoxide chemical hypoxia Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	mCx43 K<sub>ATP</sub> channels diazoxide chemical hypoxia Biology (General) QH301-705.5 Chemistry QD1-999 Michela Pecoraro Stefania Marzocco Ada Popolo Diazoxide Needs Mitochondrial Connexin43 to Exert Its Cytoprotective Effect in a Cellular Model of CoCl<sub>2</sub>-Induced Hypoxia
description	Hypoxia is the leading cause of death in cardiomyocytes. Cells respond to oxygen deprivation by activating cytoprotective programs, such as mitochondrial connexin43 (mCx43) overexpression and the opening of mitochondrial K<sub>ATP</sub> channels, aimed to reduce mitochondrial dysfunction. In this study we used an in vitro model of CoCl<sub>2</sub>-induced hypoxia to demonstrate that mCx43 and K<sub>ATP</sub> channels cooperate to induce cytoprotection. CoCl<sub>2</sub> administration induces apoptosis in H9c2 cells by increasing mitochondrial ROS production, intracellular and mitochondrial calcium overload and by inducing mitochondrial membrane depolarization. Diazoxide, an opener of K<sub>ATP</sub> channels, reduces all these deleterious effects of CoCl<sub>2</sub> only in the presence of mCx43. In fact, our results demonstrate that in the presence of radicicol, an inhibitor of Cx43 translocation to mitochondria, the cytoprotective effects of diazoxide disappear. In conclusion, these data confirm that there exists a close functional link between mCx43 and K<sub>ATP</sub> channels.
format	article
author	Michela Pecoraro Stefania Marzocco Ada Popolo
author_facet	Michela Pecoraro Stefania Marzocco Ada Popolo
author_sort	Michela Pecoraro
title	Diazoxide Needs Mitochondrial Connexin43 to Exert Its Cytoprotective Effect in a Cellular Model of CoCl<sub>2</sub>-Induced Hypoxia
title_short	Diazoxide Needs Mitochondrial Connexin43 to Exert Its Cytoprotective Effect in a Cellular Model of CoCl<sub>2</sub>-Induced Hypoxia
title_full	Diazoxide Needs Mitochondrial Connexin43 to Exert Its Cytoprotective Effect in a Cellular Model of CoCl<sub>2</sub>-Induced Hypoxia
title_fullStr	Diazoxide Needs Mitochondrial Connexin43 to Exert Its Cytoprotective Effect in a Cellular Model of CoCl<sub>2</sub>-Induced Hypoxia
title_full_unstemmed	Diazoxide Needs Mitochondrial Connexin43 to Exert Its Cytoprotective Effect in a Cellular Model of CoCl<sub>2</sub>-Induced Hypoxia
title_sort	diazoxide needs mitochondrial connexin43 to exert its cytoprotective effect in a cellular model of cocl<sub>2</sub>-induced hypoxia
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6340248dda6749b58ad770d5bd502cd4
work_keys_str_mv	AT michelapecoraro diazoxideneedsmitochondrialconnexin43toexertitscytoprotectiveeffectinacellularmodelofcoclsub2subinducedhypoxia AT stefaniamarzocco diazoxideneedsmitochondrialconnexin43toexertitscytoprotectiveeffectinacellularmodelofcoclsub2subinducedhypoxia AT adapopolo diazoxideneedsmitochondrialconnexin43toexertitscytoprotectiveeffectinacellularmodelofcoclsub2subinducedhypoxia
_version_	1718432180287307776

Diazoxide Needs Mitochondrial Connexin43 to Exert Its Cytoprotective Effect in a Cellular Model of CoCl<sub>2</sub>-Induced Hypoxia

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