Proteomic analysis of S-nitrosylation induced by 1-methyl-4-phenylpyridinium (MPP+).

Proteome Sci 2012 Dec 29;10(1):74. Epub 2012 Dec 29.

Department of Pharmacology, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nar, 634-8521, Japan.

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Background: Nitric oxide (NO) mediates its function through the direct modification of various cellular targets. S-nitrosylation is a post-translational modification of cysteine residues by NO that regulates protein function. Recently, an imbalance of S-nitrosylation has also been linked to neurodegeneration through the impairment of pro-survival proteins by S-nitrosylation.

Results: In the present study, we used two-dimensional gel electrophoresis in conjunction with the modified biotin switch assay for protein S-nitrosothiols using resin-assisted capture (SNO-RAC) to identify proteins that are S-nitrosylated more intensively in neuroblastoma cells treated with a mitochondrial complex I inhibitor, 1-methyl-4-phenylpyridinium (MPP+). We identified 14 proteins for which S-nitrosylation was upregulated and seven proteins for which it was downregulated in MPP+-treated neuroblastoma cells. Immunoblot analysis following SNO-RAC confirmed a large increase in the S-nitrosylation of esterase D (ESD), serine-threonine kinase receptor-associated protein (STRAP) and T-complex protein 1 subunit γ (TCP-1 γ) in MPP+-treated neuroblastoma cells, whereas S-nitrosylation of thioredoxin domain-containing protein 5 precursor (ERp46) was decreased.

Conclusions: These results suggest that S-nitrosylation resulting from mitochondrial dysfunction can compromise neuronal survival through altering multiple signal transduction pathways and might be a potential therapeutic target for neurodegenerative diseases.

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http://dx.doi.org/10.1186/1477-5956-10-74DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576269PMC
December 2012
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