Mitochondrial calcium, oxidative stress and apoptosis in a neurodegenerative disease model induced by 3-nitropropionic acid
Autor(a) principal: | |
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Data de Publicação: | 2004 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/27635 http://dx.doi.org/10.1046/j.1471-4159.2003.02250.x |
Resumo: | Intracellular calcium homeostasis is important for cell survival. However, increase in mitochondrial calcium (Ca-m(2+)) induces opening of permeability transition pore (PTP), mitochondrial dysfunction and apoptosis. Since alterations of intracellular Ca2+ and reactive oxygen species (ROS) generation are involved in cell death, they might be involved in neurodegenerative processes such as Huntington's disease (HD). HD is characterized by the inhibition of complex II of respiratory chain and increase in ROS production. in this report, we studied the correlation between the inhibitor of the complex II, 3-nitropropionic acid (3NP), Ca2+ metabolism, apoptosis and behavioural alterations. We showed that 3NP (1 mM) is able to release Ca-m(2+), as neither Thapsigargin (TAP, 2 muM) nor free-calcium medium affected its effect. PTP inhibitors and antioxidants inhibited this process, suggesting an increase in ROS generation and PTP opening. in addition, 3NP (0.1 mM) also induces apoptotic cell death. Behavioural changes in animals treated with 3NP (20 mg/kg/day for 4 days) were also attenuated by pre- and co-treatment with vitamin E (VE, 20 mg/kg/day). Taken together, our results show that complex II inhibition could involve Ca-m(2+) release, oxidative stress and cell death that may precede motor alterations in neurodegenerative processes such as HD. |
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Rosenstock, Tatiana Rosado [UNIFESP]Carvalho, Ana Carolina Pereira de [UNIFESP]Jurkiewicz, Aron [UNIFESP]Frussa-Filho, Roberto [UNIFESP]Smaili, Soraya Soubhi [UNIFESP]Universidade Federal de São Paulo (UNIFESP)2016-01-24T12:34:18Z2016-01-24T12:34:18Z2004-03-01Journal of Neurochemistry. Oxford: Blackwell Publishing Ltd, v. 88, n. 5, p. 1220-1228, 2004.0022-3042http://repositorio.unifesp.br/handle/11600/27635http://dx.doi.org/10.1046/j.1471-4159.2003.02250.x10.1046/j.1471-4159.2003.02250.xWOS:000189051800019Intracellular calcium homeostasis is important for cell survival. However, increase in mitochondrial calcium (Ca-m(2+)) induces opening of permeability transition pore (PTP), mitochondrial dysfunction and apoptosis. Since alterations of intracellular Ca2+ and reactive oxygen species (ROS) generation are involved in cell death, they might be involved in neurodegenerative processes such as Huntington's disease (HD). HD is characterized by the inhibition of complex II of respiratory chain and increase in ROS production. in this report, we studied the correlation between the inhibitor of the complex II, 3-nitropropionic acid (3NP), Ca2+ metabolism, apoptosis and behavioural alterations. We showed that 3NP (1 mM) is able to release Ca-m(2+), as neither Thapsigargin (TAP, 2 muM) nor free-calcium medium affected its effect. PTP inhibitors and antioxidants inhibited this process, suggesting an increase in ROS generation and PTP opening. in addition, 3NP (0.1 mM) also induces apoptotic cell death. Behavioural changes in animals treated with 3NP (20 mg/kg/day for 4 days) were also attenuated by pre- and co-treatment with vitamin E (VE, 20 mg/kg/day). Taken together, our results show that complex II inhibition could involve Ca-m(2+) release, oxidative stress and cell death that may precede motor alterations in neurodegenerative processes such as HD.Universidade Federal de São Paulo, Dept Farmacol, UNIFESP EPM, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Farmacol, UNIFESP EPM, BR-04044020 São Paulo, BrazilWeb of Science1220-1228engBlackwell Publishing LtdJournal of NeurochemistryapoptosiscalciumHuntington's diseasemitochondrianeurodegeneration3-nitropropionic acidMitochondrial calcium, oxidative stress and apoptosis in a neurodegenerative disease model induced by 3-nitropropionic acidinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/276352021-09-30 15:48:17.045metadata only accessoai:repositorio.unifesp.br:11600/27635Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652021-09-30T18:48:17Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Mitochondrial calcium, oxidative stress and apoptosis in a neurodegenerative disease model induced by 3-nitropropionic acid |
title |
Mitochondrial calcium, oxidative stress and apoptosis in a neurodegenerative disease model induced by 3-nitropropionic acid |
spellingShingle |
Mitochondrial calcium, oxidative stress and apoptosis in a neurodegenerative disease model induced by 3-nitropropionic acid Rosenstock, Tatiana Rosado [UNIFESP] apoptosis calcium Huntington's disease mitochondria neurodegeneration 3-nitropropionic acid |
title_short |
Mitochondrial calcium, oxidative stress and apoptosis in a neurodegenerative disease model induced by 3-nitropropionic acid |
title_full |
Mitochondrial calcium, oxidative stress and apoptosis in a neurodegenerative disease model induced by 3-nitropropionic acid |
title_fullStr |
Mitochondrial calcium, oxidative stress and apoptosis in a neurodegenerative disease model induced by 3-nitropropionic acid |
title_full_unstemmed |
Mitochondrial calcium, oxidative stress and apoptosis in a neurodegenerative disease model induced by 3-nitropropionic acid |
title_sort |
Mitochondrial calcium, oxidative stress and apoptosis in a neurodegenerative disease model induced by 3-nitropropionic acid |
author |
Rosenstock, Tatiana Rosado [UNIFESP] |
author_facet |
Rosenstock, Tatiana Rosado [UNIFESP] Carvalho, Ana Carolina Pereira de [UNIFESP] Jurkiewicz, Aron [UNIFESP] Frussa-Filho, Roberto [UNIFESP] Smaili, Soraya Soubhi [UNIFESP] |
author_role |
author |
author2 |
Carvalho, Ana Carolina Pereira de [UNIFESP] Jurkiewicz, Aron [UNIFESP] Frussa-Filho, Roberto [UNIFESP] Smaili, Soraya Soubhi [UNIFESP] |
author2_role |
author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Rosenstock, Tatiana Rosado [UNIFESP] Carvalho, Ana Carolina Pereira de [UNIFESP] Jurkiewicz, Aron [UNIFESP] Frussa-Filho, Roberto [UNIFESP] Smaili, Soraya Soubhi [UNIFESP] |
dc.subject.eng.fl_str_mv |
apoptosis calcium Huntington's disease mitochondria neurodegeneration 3-nitropropionic acid |
topic |
apoptosis calcium Huntington's disease mitochondria neurodegeneration 3-nitropropionic acid |
description |
Intracellular calcium homeostasis is important for cell survival. However, increase in mitochondrial calcium (Ca-m(2+)) induces opening of permeability transition pore (PTP), mitochondrial dysfunction and apoptosis. Since alterations of intracellular Ca2+ and reactive oxygen species (ROS) generation are involved in cell death, they might be involved in neurodegenerative processes such as Huntington's disease (HD). HD is characterized by the inhibition of complex II of respiratory chain and increase in ROS production. in this report, we studied the correlation between the inhibitor of the complex II, 3-nitropropionic acid (3NP), Ca2+ metabolism, apoptosis and behavioural alterations. We showed that 3NP (1 mM) is able to release Ca-m(2+), as neither Thapsigargin (TAP, 2 muM) nor free-calcium medium affected its effect. PTP inhibitors and antioxidants inhibited this process, suggesting an increase in ROS generation and PTP opening. in addition, 3NP (0.1 mM) also induces apoptotic cell death. Behavioural changes in animals treated with 3NP (20 mg/kg/day for 4 days) were also attenuated by pre- and co-treatment with vitamin E (VE, 20 mg/kg/day). Taken together, our results show that complex II inhibition could involve Ca-m(2+) release, oxidative stress and cell death that may precede motor alterations in neurodegenerative processes such as HD. |
publishDate |
2004 |
dc.date.issued.fl_str_mv |
2004-03-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T12:34:18Z |
dc.date.available.fl_str_mv |
2016-01-24T12:34:18Z |
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.citation.fl_str_mv |
Journal of Neurochemistry. Oxford: Blackwell Publishing Ltd, v. 88, n. 5, p. 1220-1228, 2004. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/27635 http://dx.doi.org/10.1046/j.1471-4159.2003.02250.x |
dc.identifier.issn.none.fl_str_mv |
0022-3042 |
dc.identifier.doi.none.fl_str_mv |
10.1046/j.1471-4159.2003.02250.x |
dc.identifier.wos.none.fl_str_mv |
WOS:000189051800019 |
identifier_str_mv |
Journal of Neurochemistry. Oxford: Blackwell Publishing Ltd, v. 88, n. 5, p. 1220-1228, 2004. 0022-3042 10.1046/j.1471-4159.2003.02250.x WOS:000189051800019 |
url |
http://repositorio.unifesp.br/handle/11600/27635 http://dx.doi.org/10.1046/j.1471-4159.2003.02250.x |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Journal of Neurochemistry |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1220-1228 |
dc.publisher.none.fl_str_mv |
Blackwell Publishing Ltd |
publisher.none.fl_str_mv |
Blackwell Publishing Ltd |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764168437170176 |