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Oxidative modification of mitochondrial proteins and cell death in Parkinson's disease
Author(s) -
Maruyama W.,
Naoi M.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.42_6.x
Subject(s) - oxidative stress , peroxynitrite , mitochondrion , oxidative phosphorylation , nitrotyrosine , programmed cell death , reactive oxygen species , reactive nitrogen species , mitochondrial respiratory chain , microbiology and biotechnology , chemistry , neurodegeneration , biochemistry , lewy body , rotenone , biology , parkinson's disease , apoptosis , superoxide , medicine , enzyme , pathology , nitric oxide synthase , disease
Oxidative stress is one of the cell death mechanisms in neurodegenerative disorders, such as Parkinson's disease (PD) and Alzheimer's disease. Most of reactive oxygen species (ROS) generate in mitochondria through oxidative phosphorylation, and a part of them are not scavenged by antioxidative system and react with bioactive molecules. Recently, alpha‐synuclein containing nitrotyrosine, a marker for oxidative modification by peroxynitrite, was identified in Lewy body. In addition, inhibitors of mitochondrial respiratory chain were reported to induce formation of Lewy body‐like inclusion in vivo and in vitro . In this paper it was examined whether ROS and reactive nitrogen species (RNS) generated in mitochondria oxidize mitochondrial respiratory enzymes and induce the formation of inclusion body and cell death in PD. Human neuroblastoma SH‐SY5Y cells were treated with a peroxynitrite donor, SIN‐1, or an inhibitor of complex I, rotenone. After the treatment, proteins modified with toxic aldehydes, 4‐hydroxynonenal and acrolein, and containing nitrotyrosine were analyzed by immunoblotting. Particularly in mitochondrial fraction, the oxidized protein was characterized by two‐dimensional immunoblotting. Most of the oxidized proteins were detected in subunits proteins of complex I. These results indicate that mitochondrial complex I is a main target of oxidative stress in dopamine neurons and its dysfunction may be involved in the death mechanism in neurodegenerative disorders.