Differential involvement of mitochondrial permeability transition in cytotoxicity of 1-methyl-4-phenylpyridinium and 6-hydroxydopamine.

Molecular and Cellular Biochemistry
Chung Soo LeeEun Sook Han

Abstract

Defects in mitochondrial function have been shown to participate in the induction of neuronal cell injury. The aim of the present study was to assess the influence of the mitochondrial membrane permeability transition inhibition against the toxicity of 1-methyl-4-phenylpyridinium (MPP(+)) and 6-hydroxydopamine (6-OHDA) in relation to the mitochondria-mediated cell death process and role of oxidative stress. Both MPP(+) and 6-OHDA induced the nuclear damage, the changes in the mitochondrial membrane permeability, leading to the cytochrome c release and caspase-3 activation, the formation of reactive oxygen species and the depletion of GSH in differentiated PC12 cells. Cyclosporin A (CsA), trifluoperazine and aristolochic acid, inhibitors of mitochondrial permeability transition, significantly attenuated the MPP(+)-induced mitochondrial damage leading to caspase-3 activation, increased oxidative stress and cell death. In contrast to MPP(+), the cytotoxicity of 6-OHDA was not reduced by the addition of the mitochondrial permeability transition inhibitors. The results show that the cytotoxicity of MPP(+) may be mediated by the mitochondrial permeability transition formation, which is associated with formation of reactive oxygen spe...Continue Reading

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Citations

Jan 20, 2010·Clinical and Experimental Pharmacology & Physiology·Hua-Pei SongYue-Sheng Huang
Nov 15, 2007·Antioxidants & Redox Signaling·Hazel H Szeto
Aug 12, 2009·The FEBS Journal·Anna SandebringAngel Cedazo-Mínguez
Dec 17, 2008·Annals of the New York Academy of Sciences·Hazel H Szeto
Nov 13, 2013·International Journal of Molecular Sciences·Ruben K DagdaElzbieta Janda
Jul 31, 2008·Journal of Neurochemistry·Jezabel Rodriguez-BlancoCarmen Rodriguez
Sep 30, 2009·British Journal of Pharmacology·Sergio Perez-AlvarezMaría F Galindo
Nov 3, 2020·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Ryosuke TatsunamiKeisuke Sato

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