Myocardial and mitochondrial effects of the anhydrase carbonic inhibitor ethoxzolamide in ischemia‐reperfusion

Abstract We have previously demonstrated that inhibition of extracellularly oriented carbonic anhydrase (CA) isoforms protects the myocardium against ischemia‐reperfusion injury. In this study, our aim was to assess the possible further contribution of CA intracellular isoforms examining the actions...

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Autores principales:	Alejandro Ciocci Pardo, Luisa F. González Arbeláez, Juliana C. Fantinelli, Bernardo V. Álvarez, Susana M. Mosca, Erik R. Swenson
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	carbonic anhydrase ethoxzolamide ischemia‐reperfusion mitochondria myocardium p38MAPK Physiology QP1-981
Acceso en línea:	https://doaj.org/article/7d2166fa400c440bad93b484c3d0272a
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spelling	oai:doaj.org-article:7d2166fa400c440bad93b484c3d0272a2021-11-27T15:48:30ZMyocardial and mitochondrial effects of the anhydrase carbonic inhibitor ethoxzolamide in ischemia‐reperfusion2051-817X10.14814/phy2.15093https://doaj.org/article/7d2166fa400c440bad93b484c3d0272a2021-11-01T00:00:00Zhttps://doi.org/10.14814/phy2.15093https://doaj.org/toc/2051-817XAbstract We have previously demonstrated that inhibition of extracellularly oriented carbonic anhydrase (CA) isoforms protects the myocardium against ischemia‐reperfusion injury. In this study, our aim was to assess the possible further contribution of CA intracellular isoforms examining the actions of the highly diffusible cell membrane permeant inhibitor of CA, ethoxzolamide (ETZ). Isolated rat hearts, after 20 min of stabilization, were assigned to the following groups: (1) Nonischemic control: 90 min of perfusion; (2) Ischemic control: 30 min of global ischemia and 60 min of reperfusion (R); and (3) ETZ: ETZ at a concentration of 100 μM was administered for 10 min before the onset of ischemia and then during the first 10 min of reperfusion. In additional groups, ETZ was administered in the presence of SB202190 (SB, a p38MAPK inhibitor) or chelerythrine (Chel, a protein kinase C [PKC] inhibitor). Infarct size, myocardial function, and the expression of phosphorylated forms of p38MAPK, PKCε, HSP27, and Drp1, and calcineurin Aβ content were assessed. In isolated mitochondria, the Ca2+ response, Ca2+ retention capacity, and membrane potential were measured. ETZ decreased infarct size by 60%, improved postischemic recovery of myocardial contractile and diastolic relaxation increased P‐p38MAPK, P‐PKCε, P‐HSP27, and P‐Drp1 expression, decreased calcineurin content, and normalized calcium and membrane potential parameters measured in isolated mitochondria. These effects were significantly attenuated when ETZ was administered in the presence of SB or Chel. These data show that ETZ protects the myocardium and mitochondria against ischemia‐reperfusion injury through p38MAPK‐ and PKCε‐dependent pathways and reinforces the role of CA as a possible target in the management of acute cardiac ischemic diseases.Alejandro Ciocci PardoLuisa F. González ArbeláezJuliana C. FantinelliBernardo V. ÁlvarezSusana M. MoscaErik R. SwensonWileyarticlecarbonic anhydraseethoxzolamideischemia‐reperfusionmitochondriamyocardiump38MAPKPhysiologyQP1-981ENPhysiological Reports, Vol 9, Iss 22, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	carbonic anhydrase ethoxzolamide ischemia‐reperfusion mitochondria myocardium p38MAPK Physiology QP1-981
spellingShingle	carbonic anhydrase ethoxzolamide ischemia‐reperfusion mitochondria myocardium p38MAPK Physiology QP1-981 Alejandro Ciocci Pardo Luisa F. González Arbeláez Juliana C. Fantinelli Bernardo V. Álvarez Susana M. Mosca Erik R. Swenson Myocardial and mitochondrial effects of the anhydrase carbonic inhibitor ethoxzolamide in ischemia‐reperfusion
description	Abstract We have previously demonstrated that inhibition of extracellularly oriented carbonic anhydrase (CA) isoforms protects the myocardium against ischemia‐reperfusion injury. In this study, our aim was to assess the possible further contribution of CA intracellular isoforms examining the actions of the highly diffusible cell membrane permeant inhibitor of CA, ethoxzolamide (ETZ). Isolated rat hearts, after 20 min of stabilization, were assigned to the following groups: (1) Nonischemic control: 90 min of perfusion; (2) Ischemic control: 30 min of global ischemia and 60 min of reperfusion (R); and (3) ETZ: ETZ at a concentration of 100 μM was administered for 10 min before the onset of ischemia and then during the first 10 min of reperfusion. In additional groups, ETZ was administered in the presence of SB202190 (SB, a p38MAPK inhibitor) or chelerythrine (Chel, a protein kinase C [PKC] inhibitor). Infarct size, myocardial function, and the expression of phosphorylated forms of p38MAPK, PKCε, HSP27, and Drp1, and calcineurin Aβ content were assessed. In isolated mitochondria, the Ca2+ response, Ca2+ retention capacity, and membrane potential were measured. ETZ decreased infarct size by 60%, improved postischemic recovery of myocardial contractile and diastolic relaxation increased P‐p38MAPK, P‐PKCε, P‐HSP27, and P‐Drp1 expression, decreased calcineurin content, and normalized calcium and membrane potential parameters measured in isolated mitochondria. These effects were significantly attenuated when ETZ was administered in the presence of SB or Chel. These data show that ETZ protects the myocardium and mitochondria against ischemia‐reperfusion injury through p38MAPK‐ and PKCε‐dependent pathways and reinforces the role of CA as a possible target in the management of acute cardiac ischemic diseases.
format	article
author	Alejandro Ciocci Pardo Luisa F. González Arbeláez Juliana C. Fantinelli Bernardo V. Álvarez Susana M. Mosca Erik R. Swenson
author_facet	Alejandro Ciocci Pardo Luisa F. González Arbeláez Juliana C. Fantinelli Bernardo V. Álvarez Susana M. Mosca Erik R. Swenson
author_sort	Alejandro Ciocci Pardo
title	Myocardial and mitochondrial effects of the anhydrase carbonic inhibitor ethoxzolamide in ischemia‐reperfusion
title_short	Myocardial and mitochondrial effects of the anhydrase carbonic inhibitor ethoxzolamide in ischemia‐reperfusion
title_full	Myocardial and mitochondrial effects of the anhydrase carbonic inhibitor ethoxzolamide in ischemia‐reperfusion
title_fullStr	Myocardial and mitochondrial effects of the anhydrase carbonic inhibitor ethoxzolamide in ischemia‐reperfusion
title_full_unstemmed	Myocardial and mitochondrial effects of the anhydrase carbonic inhibitor ethoxzolamide in ischemia‐reperfusion
title_sort	myocardial and mitochondrial effects of the anhydrase carbonic inhibitor ethoxzolamide in ischemia‐reperfusion
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/7d2166fa400c440bad93b484c3d0272a
work_keys_str_mv	AT alejandrocioccipardo myocardialandmitochondrialeffectsoftheanhydrasecarbonicinhibitorethoxzolamideinischemiareperfusion AT luisafgonzalezarbelaez myocardialandmitochondrialeffectsoftheanhydrasecarbonicinhibitorethoxzolamideinischemiareperfusion AT julianacfantinelli myocardialandmitochondrialeffectsoftheanhydrasecarbonicinhibitorethoxzolamideinischemiareperfusion AT bernardovalvarez myocardialandmitochondrialeffectsoftheanhydrasecarbonicinhibitorethoxzolamideinischemiareperfusion AT susanammosca myocardialandmitochondrialeffectsoftheanhydrasecarbonicinhibitorethoxzolamideinischemiareperfusion AT erikrswenson myocardialandmitochondrialeffectsoftheanhydrasecarbonicinhibitorethoxzolamideinischemiareperfusion
_version_	1718408511693520896

Myocardial and mitochondrial effects of the anhydrase carbonic inhibitor ethoxzolamide in ischemia‐reperfusion

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