Chenodeoxycholate induction of mitochondrial permeability transition pore is associated with increased membrane fluidity and cytochrome c release: protective role of carvedilol

Detalhes bibliográficos
Autor(a) principal: Rolo, Anabela P.
Data de Publicação: 2003
Outros Autores: Oliveira, Paulo J., Moreno, António J., Palmeira, Carlos M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/5405
https://doi.org/10.1016/S1567-7249(03)00007-2
Resumo: Chenodeoxycholate (CDCA) is a primary bile acid mostly implicated in cholestatic liver injury. In this study, we have investigated the involvement of membrane fluidity and cytochrome c release in CDCA-induced mitochondrial permeability transition (MPT), and the preventive role of carvedilol. Treatment of calcium-loaded hepatic mitochondria with CDCA was found to cause osmotic swelling and release of cytochrome c, associated with an increase in membrane fluidity, in both protein and lipid regions. Carvedilol and cyclosporine A (CyA) reduced both cytochrome c release and alterations in membrane fluidity induced by CDCA. The hydroxylated metabolite of carvedilol, BM-910228, had no effect. Thus, modulation of membrane fluidity, plays an important role in MPT pore opening promoted by CDCA. As a result, we have delineated a pathway for the preventive role of carvedilol in mitochondrial dysfunction induced by CDCA.
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spelling Chenodeoxycholate induction of mitochondrial permeability transition pore is associated with increased membrane fluidity and cytochrome c release: protective role of carvedilolChenodeoxycholateCarvedilolMitochondriaCholestasisCardiomyopathyMitochondrial permeability transitionMembrane fluidityChenodeoxycholate (CDCA) is a primary bile acid mostly implicated in cholestatic liver injury. In this study, we have investigated the involvement of membrane fluidity and cytochrome c release in CDCA-induced mitochondrial permeability transition (MPT), and the preventive role of carvedilol. Treatment of calcium-loaded hepatic mitochondria with CDCA was found to cause osmotic swelling and release of cytochrome c, associated with an increase in membrane fluidity, in both protein and lipid regions. Carvedilol and cyclosporine A (CyA) reduced both cytochrome c release and alterations in membrane fluidity induced by CDCA. The hydroxylated metabolite of carvedilol, BM-910228, had no effect. Thus, modulation of membrane fluidity, plays an important role in MPT pore opening promoted by CDCA. As a result, we have delineated a pathway for the preventive role of carvedilol in mitochondrial dysfunction induced by CDCA.http://www.sciencedirect.com/science/article/B6W8G-480CGK0-1/1/081a86d56a239d32c5933f92219300ba2003info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/5405http://hdl.handle.net/10316/5405https://doi.org/10.1016/S1567-7249(03)00007-2engMitochondrion. 2:4 (2003) 305-311Rolo, Anabela P.Oliveira, Paulo J.Moreno, António J.Palmeira, Carlos M.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2021-10-07T10:32:19Zoai:estudogeral.uc.pt:10316/5405Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:55:39.028429Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Chenodeoxycholate induction of mitochondrial permeability transition pore is associated with increased membrane fluidity and cytochrome c release: protective role of carvedilol
title Chenodeoxycholate induction of mitochondrial permeability transition pore is associated with increased membrane fluidity and cytochrome c release: protective role of carvedilol
spellingShingle Chenodeoxycholate induction of mitochondrial permeability transition pore is associated with increased membrane fluidity and cytochrome c release: protective role of carvedilol
Rolo, Anabela P.
Chenodeoxycholate
Carvedilol
Mitochondria
Cholestasis
Cardiomyopathy
Mitochondrial permeability transition
Membrane fluidity
title_short Chenodeoxycholate induction of mitochondrial permeability transition pore is associated with increased membrane fluidity and cytochrome c release: protective role of carvedilol
title_full Chenodeoxycholate induction of mitochondrial permeability transition pore is associated with increased membrane fluidity and cytochrome c release: protective role of carvedilol
title_fullStr Chenodeoxycholate induction of mitochondrial permeability transition pore is associated with increased membrane fluidity and cytochrome c release: protective role of carvedilol
title_full_unstemmed Chenodeoxycholate induction of mitochondrial permeability transition pore is associated with increased membrane fluidity and cytochrome c release: protective role of carvedilol
title_sort Chenodeoxycholate induction of mitochondrial permeability transition pore is associated with increased membrane fluidity and cytochrome c release: protective role of carvedilol
author Rolo, Anabela P.
author_facet Rolo, Anabela P.
Oliveira, Paulo J.
Moreno, António J.
Palmeira, Carlos M.
author_role author
author2 Oliveira, Paulo J.
Moreno, António J.
Palmeira, Carlos M.
author2_role author
author
author
dc.contributor.author.fl_str_mv Rolo, Anabela P.
Oliveira, Paulo J.
Moreno, António J.
Palmeira, Carlos M.
dc.subject.por.fl_str_mv Chenodeoxycholate
Carvedilol
Mitochondria
Cholestasis
Cardiomyopathy
Mitochondrial permeability transition
Membrane fluidity
topic Chenodeoxycholate
Carvedilol
Mitochondria
Cholestasis
Cardiomyopathy
Mitochondrial permeability transition
Membrane fluidity
description Chenodeoxycholate (CDCA) is a primary bile acid mostly implicated in cholestatic liver injury. In this study, we have investigated the involvement of membrane fluidity and cytochrome c release in CDCA-induced mitochondrial permeability transition (MPT), and the preventive role of carvedilol. Treatment of calcium-loaded hepatic mitochondria with CDCA was found to cause osmotic swelling and release of cytochrome c, associated with an increase in membrane fluidity, in both protein and lipid regions. Carvedilol and cyclosporine A (CyA) reduced both cytochrome c release and alterations in membrane fluidity induced by CDCA. The hydroxylated metabolite of carvedilol, BM-910228, had no effect. Thus, modulation of membrane fluidity, plays an important role in MPT pore opening promoted by CDCA. As a result, we have delineated a pathway for the preventive role of carvedilol in mitochondrial dysfunction induced by CDCA.
publishDate 2003
dc.date.none.fl_str_mv 2003
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10316/5405
http://hdl.handle.net/10316/5405
https://doi.org/10.1016/S1567-7249(03)00007-2
url http://hdl.handle.net/10316/5405
https://doi.org/10.1016/S1567-7249(03)00007-2
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Mitochondrion. 2:4 (2003) 305-311
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eu_rights_str_mv openAccess
dc.format.none.fl_str_mv aplication/PDF
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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