Membrane structural changes support the involvement of mitochondria in the bile salt-induced apoptosis of rat hepatocytes

Detalhes bibliográficos
Autor(a) principal: Solá, Susana
Data de Publicação: 2002
Outros Autores: Brito, Maria A., Brites, Dora, Moura, José J. G., Rodrigues, Cecília
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/8715
Resumo: Clin Sci (Lond). 2002 Nov;103(5):475-85
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spelling Membrane structural changes support the involvement of mitochondria in the bile salt-induced apoptosis of rat hepatocytesClin Sci (Lond). 2002 Nov;103(5):475-85The accumulation of toxic bile salts within the hepatocyte plays a key role in organ injury during liver disease. Deoxycholate (DC) and glycochenodeoxycholate (GCDC) induce apoptosis in vitro and in vivo, perhaps through direct perturbation of mitochondrial membrane structure and function. In contrast, ursodeoxycholate (UDC) and its taurine-conjugated form (TUDC) appear to be protective. We show here that hydrophobic bile salts induced apoptosis in cultured rat hepatocytes, without modulating the expression of pro-apoptotic Bax protein, and caused cytochrome c release in isolated mitochondria. Co-incubation with UDC and TUDC prevented cell death and efflux of mitochondrial factors. Using spin-labelling techniques and EPR spectroscopy analysis of isolated rat liver mitochondria, we found signi®cant structural changes at the membrane±water surface in mitochondria exposed to hydrophobic bile salts, including modi®ed lipid polarity and ¯uidity, altered protein order and increased oxidative injury. UDC, TUDC and cyclosporin A almost completely abrogated DC- and GCDC-induced membrane perturbations. We conclude that the toxicity of hydrophobic bile salts to hepatocytes is mediated by cytochrome c release, through a mechanism associated with marked direct effects on mitochondrial membrane lipid polarity and ¯uidity, protein order and redox status, without modulation of pro-apoptotic Bax expression. UDC and TUDC can directly suppress disruption of mitochondrial membrane structure, which may represent an important mechanism of hepatoprotection by these bile salts.The Biochemical Society and the Medical Research SocietyRUNSolá, SusanaBrito, Maria A.Brites, DoraMoura, José J. G.Rodrigues, Cecília2013-02-06T14:49:23Z20022002-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/8715enginfo: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:RCAAP2024-03-11T03:41:36Zoai:run.unl.pt:10362/8715Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:18:23.758192Repositório 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 Membrane structural changes support the involvement of mitochondria in the bile salt-induced apoptosis of rat hepatocytes
title Membrane structural changes support the involvement of mitochondria in the bile salt-induced apoptosis of rat hepatocytes
spellingShingle Membrane structural changes support the involvement of mitochondria in the bile salt-induced apoptosis of rat hepatocytes
Solá, Susana
title_short Membrane structural changes support the involvement of mitochondria in the bile salt-induced apoptosis of rat hepatocytes
title_full Membrane structural changes support the involvement of mitochondria in the bile salt-induced apoptosis of rat hepatocytes
title_fullStr Membrane structural changes support the involvement of mitochondria in the bile salt-induced apoptosis of rat hepatocytes
title_full_unstemmed Membrane structural changes support the involvement of mitochondria in the bile salt-induced apoptosis of rat hepatocytes
title_sort Membrane structural changes support the involvement of mitochondria in the bile salt-induced apoptosis of rat hepatocytes
author Solá, Susana
author_facet Solá, Susana
Brito, Maria A.
Brites, Dora
Moura, José J. G.
Rodrigues, Cecília
author_role author
author2 Brito, Maria A.
Brites, Dora
Moura, José J. G.
Rodrigues, Cecília
author2_role author
author
author
author
dc.contributor.none.fl_str_mv RUN
dc.contributor.author.fl_str_mv Solá, Susana
Brito, Maria A.
Brites, Dora
Moura, José J. G.
Rodrigues, Cecília
description Clin Sci (Lond). 2002 Nov;103(5):475-85
publishDate 2002
dc.date.none.fl_str_mv 2002
2002-01-01T00:00:00Z
2013-02-06T14:49:23Z
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/10362/8715
url http://hdl.handle.net/10362/8715
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv The Biochemical Society and the Medical Research Society
publisher.none.fl_str_mv The Biochemical Society and the Medical Research Society
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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