Mitochondrial calcium, oxidative stress and apoptosis in a neurodegenerative disease model induced by 3-nitropropionic acid

Mitochondrial calcium, oxidative stress and apoptosis in a neurodegenerative disease model induced by 3-nitropropionic acid

Autor Rosenstock, Tatiana Rosado Autor UNIFESP Google Scholar
Carvalho, Ana Carolina Pereira de Autor UNIFESP Google Scholar
Jurkiewicz, Aron Autor UNIFESP Google Scholar
Frussa-Filho, Roberto Autor UNIFESP Google Scholar
Smaili, Soraya Soubhi Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
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.
Assunto apoptosis
calcium
Huntington's disease
mitochondria
neurodegeneration
3-nitropropionic acid
Idioma Inglês
Data 2004-03-01
Publicado em Journal of Neurochemistry. Oxford: Blackwell Publishing Ltd, v. 88, n. 5, p. 1220-1228, 2004.
ISSN 0022-3042 (Sherpa/Romeo, fator de impacto)
Editor Blackwell Publishing Ltd
Extensão 1220-1228
Fonte http://dx.doi.org/10.1046/j.1471-4159.2003.02250.x
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000189051800019
URI http://repositorio.unifesp.br/handle/11600/27635

Mostrar registro completo




Arquivos deste item

Arquivos Tamanho Formato Visualização

Não existem arquivos associados a este item.

Este item aparece na(s) seguinte(s) coleção(s)