Neuromelanin selectively induces apoptosis in dopaminergic SH-SY5Y cells by deglutathionylation in mitochondria: involvement of the protein and melanin component

Journal of Neurochemistry
M NaoiPeter Riederer

Abstract

Parkinson's disease (PD) is characterized by selective depletion of nigral dopamine (DA) neurons containing neuromelanin (NM), suggesting the involvement of NM in the pathogenesis. This study reports induction of apoptosis by NM in SH-SY5Y cells, whereas protease-K-treated NM, synthesized DA- and cysteinyl dopamine melanin showed much less cytotoxicity. Cell death was mediated by mitochondria-mediated apoptotic pathway, namely collapse of mitochondrial membrane potential, release of cytochrome c, and activation of caspase 3, but Bcl-2 over-expression did not suppress apoptosis. NM increased sulfhydryl content in mitochondria, and a major part of it was identified as GSH, whereas dopamine melanin significantly reduced sulfhydryl levels. Western blot analysis for protein-bound GSH demonstrated that only NM reduced S-glutathionylated proteins in mitochondria and dissociated macromolecular structure of complex I. Reactive oxygen and nitrogen species were required for the deglutathionylation by NM, which antioxidants reduced significantly with prevention of apoptosis. These results suggest that NM may be related to cell death of DA neurons in PD and aging through regulation of mitochondrial redox state and S-glutathionylation, for w...Continue Reading

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Citations

Jul 24, 2012·Antioxidants & Redox Signaling·Humberto Rodriguez-RochaRodrigo Franco
Mar 1, 2012·Antioxidants & Redox Signaling·Aracely Garcia-GarciaRodrigo Franco
Apr 26, 2012·Antioxidants & Redox Signaling·Fei YinEnrique Cadenas
Sep 12, 2012·Parkinson's Disease·Patricia MuñozJuan Segura-Aguilar
Jun 27, 2012·Biochimica Et Biophysica Acta·Magdalena L Circu, Tak Yee Aw
Aug 14, 2009·Expert Review of Neurotherapeutics·Makoto Naoi, Wakako Maruyama
Sep 8, 2010·Free Radical Research·Isabella Dalle-DonneAldo Milzani
Apr 22, 2015·The Biochemical Journal·David J McGarryColin J Henderson
Dec 9, 2010·Journal of Neurochemistry·Jeswinder Sian-HülsmannPeter Riederer

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