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

Author 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
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract 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.
Keywords apoptosis
calcium
Huntington's disease
mitochondria
neurodegeneration
3-nitropropionic acid
Language English
Date 2004-03-01
Published in Journal of Neurochemistry. Oxford: Blackwell Publishing Ltd, v. 88, n. 5, p. 1220-1228, 2004.
ISSN 0022-3042 (Sherpa/Romeo, impact factor)
Publisher Blackwell Publishing Ltd
Extent 1220-1228
Origin http://dx.doi.org/10.1046/j.1471-4159.2003.02250.x
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000189051800019
URI http://repositorio.unifesp.br/handle/11600/27635

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