Selective nitration of mitochondrial complex I by peroxynitrite: involvement in mitochondria dysfunction and cell death of dopaminergic SH-SY5Y cells
- 1 January 2002
- journal article
- Published by Springer Nature in Journal Of Neural Transmission-Parkinsons Disease and Dementia Section
- Vol. 109 (1) , 1-13
- https://doi.org/10.1007/s702-002-8232-1
Abstract
3-Nitrotyrosine (3-NT) is a specific marker of protein nitration by peroxynitrite (ONOO−) produced from nitric oxide and superoxide. Increase in 3-NT containing protein (3-NT protein) was reported in brains from patients with some neurodegenerative disorders and aging. In this paper, intracellular localization of 3-NT protein was examined in dopaminergic SH-SY5Y cells using the selective antibody against protein-bound 3-NT. 3-NT protein was detected in plasma membrane/nucleus and mitochondria fractions, and interestingly in polypeptide composition of mitochondrial complex I. ONOO−-generating SIN-1 induced apoptotic cell death with concomitant increase in 3-NT protein and reduction in mitochondrial ATP synthesis. In addition, an inhibitor of proteasomes, carbobenzoxy-L-isoleucyl-γ-t-butyl-L-glutamyl-L-alanyl-L-leucinal, enhanced the effects of ONOO−. These results suggest that ONOO− may induce mitochondrial dysfunction and cell death in neurons through nitration of mitochondrial complex I subunits.Keywords
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