Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondria
Autor(a) principal: | |
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Data de Publicação: | 2002 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/1677 |
Resumo: | Background/Aims: Unconjugated bilirubin (UCB) impairs crucial aspects of cell function and induces apoptosis in primary cultured neurones. While mechanisms of cytotoxicity begin to unfold, mitochondria appear as potential primary targets. Methods: We used electron paramagnetic resonance spectroscopy analysis of isolated rat mitochondria to test the hypothesis that UCB physically interacts with mitochondria to induce structural membrane perturbation, leading to increased permeability, and subsequent release of apoptotic factors. Results: Our data demonstrate profound changes on mitochondrial membrane properties during incubation with UCB, including modified membrane lipid polarity and fluidity (P , 0:01), as well as disrupted protein mobility(P , 0:001). Consistent with increased permeability, cytochrome c was released from the intermembrane space(P , 0:01), perhaps uncoupling the respiratory chain and further increasing oxidative stress (P , 0:01). Both ursodeoxycholate, a mitochondrial-membrane stabilising agent, and cyclosporine A, an inhibitor of the permeability transition, almost completely abrogated UCB-induced perturbation. Conclusions: UCB directly interacts with mitochondria influencing membrane lipid and protein properties, redox status, and cytochrome c content. Thus, apoptosis induced by UCB may be mediated, at least in part, by physical perturbation of the mitochondrial membrane. These novel findings should ultimately prove useful to our evolving understanding of UCB cytotoxicity. |
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7160 |
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Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondriaBilirubin cytotoxicityCytochrome cElectron paramagnetic resonance spectroscopyMitochondrial membrane structureBackground/Aims: Unconjugated bilirubin (UCB) impairs crucial aspects of cell function and induces apoptosis in primary cultured neurones. While mechanisms of cytotoxicity begin to unfold, mitochondria appear as potential primary targets. Methods: We used electron paramagnetic resonance spectroscopy analysis of isolated rat mitochondria to test the hypothesis that UCB physically interacts with mitochondria to induce structural membrane perturbation, leading to increased permeability, and subsequent release of apoptotic factors. Results: Our data demonstrate profound changes on mitochondrial membrane properties during incubation with UCB, including modified membrane lipid polarity and fluidity (P , 0:01), as well as disrupted protein mobility(P , 0:001). Consistent with increased permeability, cytochrome c was released from the intermembrane space(P , 0:01), perhaps uncoupling the respiratory chain and further increasing oxidative stress (P , 0:01). Both ursodeoxycholate, a mitochondrial-membrane stabilising agent, and cyclosporine A, an inhibitor of the permeability transition, almost completely abrogated UCB-induced perturbation. Conclusions: UCB directly interacts with mitochondria influencing membrane lipid and protein properties, redox status, and cytochrome c content. Thus, apoptosis induced by UCB may be mediated, at least in part, by physical perturbation of the mitochondrial membrane. These novel findings should ultimately prove useful to our evolving understanding of UCB cytotoxicity.Elsevier Science B.V.RUNMoura, José J. G.Rodrigues, Cecília M. P.Solá, SusanaBrito, Maria A.Brites, Dora2008-10-16T11:59:47Z20022002-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/1677eng0168-8278info: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:RCAAP2024-03-11T03:31:40Zoai:run.unl.pt:10362/1677Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:14:47.730280Repositório 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 |
Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondria |
title |
Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondria |
spellingShingle |
Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondria Moura, José J. G. Bilirubin cytotoxicity Cytochrome c Electron paramagnetic resonance spectroscopy Mitochondrial membrane structure |
title_short |
Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondria |
title_full |
Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondria |
title_fullStr |
Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondria |
title_full_unstemmed |
Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondria |
title_sort |
Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondria |
author |
Moura, José J. G. |
author_facet |
Moura, José J. G. Rodrigues, Cecília M. P. Solá, Susana Brito, Maria A. Brites, Dora |
author_role |
author |
author2 |
Rodrigues, Cecília M. P. Solá, Susana Brito, Maria A. Brites, Dora |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
RUN |
dc.contributor.author.fl_str_mv |
Moura, José J. G. Rodrigues, Cecília M. P. Solá, Susana Brito, Maria A. Brites, Dora |
dc.subject.por.fl_str_mv |
Bilirubin cytotoxicity Cytochrome c Electron paramagnetic resonance spectroscopy Mitochondrial membrane structure |
topic |
Bilirubin cytotoxicity Cytochrome c Electron paramagnetic resonance spectroscopy Mitochondrial membrane structure |
description |
Background/Aims: Unconjugated bilirubin (UCB) impairs crucial aspects of cell function and induces apoptosis in primary cultured neurones. While mechanisms of cytotoxicity begin to unfold, mitochondria appear as potential primary targets. Methods: We used electron paramagnetic resonance spectroscopy analysis of isolated rat mitochondria to test the hypothesis that UCB physically interacts with mitochondria to induce structural membrane perturbation, leading to increased permeability, and subsequent release of apoptotic factors. Results: Our data demonstrate profound changes on mitochondrial membrane properties during incubation with UCB, including modified membrane lipid polarity and fluidity (P , 0:01), as well as disrupted protein mobility(P , 0:001). Consistent with increased permeability, cytochrome c was released from the intermembrane space(P , 0:01), perhaps uncoupling the respiratory chain and further increasing oxidative stress (P , 0:01). Both ursodeoxycholate, a mitochondrial-membrane stabilising agent, and cyclosporine A, an inhibitor of the permeability transition, almost completely abrogated UCB-induced perturbation. Conclusions: UCB directly interacts with mitochondria influencing membrane lipid and protein properties, redox status, and cytochrome c content. Thus, apoptosis induced by UCB may be mediated, at least in part, by physical perturbation of the mitochondrial membrane. These novel findings should ultimately prove useful to our evolving understanding of UCB cytotoxicity. |
publishDate |
2002 |
dc.date.none.fl_str_mv |
2002 2002-01-01T00:00:00Z 2008-10-16T11:59:47Z |
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/10362/1677 |
url |
http://hdl.handle.net/10362/1677 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0168-8278 |
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 |
Elsevier Science B.V. |
publisher.none.fl_str_mv |
Elsevier Science B.V. |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
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1799137800320188416 |