Contract Grant Sponsor: Parkinson's UK, London, UK.
Neuroprotective Effects of Nicotinamide N-Methyltransferase and its Metabolite 1-Methylnicotinamide
Article first published online: 18 JUL 2013
© 2013 Wiley Periodicals, Inc.
Journal of Biochemical and Molecular Toxicology
Volume 27, Issue 9, pages 451–456, September 2013
How to Cite
Milani, Z. H., Ramsden, D. B. and Parsons, R. B. (2013), Neuroprotective Effects of Nicotinamide N-Methyltransferase and its Metabolite 1-Methylnicotinamide. J. Biochem. Mol. Toxicol., 27: 451–456. doi: 10.1002/jbt.21508
Contract Grant Number: Grant Reference 0505.
Contract Grant Sponsor: United Hospitals Charity, Birmingham, UK.
- Issue published online: 4 SEP 2013
- Article first published online: 18 JUL 2013
- Manuscript Accepted: 21 JUN 2013
- Manuscript Revised: 7 JUN 2013
- Manuscript Received: 15 APR 2013
- Parkinson's UK, London, UK. Grant Number: 0505
- United Hospitals Charity, Birmingham, UK
- Nicotinamide N-methyltransferase;
- Complex I;
- ATP Synthesis
Nicotinamide N-methyltransferase (NNMT, E.C. 126.96.36.199) catalyses the N-methylation of nicotinamide to 1-methylnicotinamide (MeN). We have previously shown that the ectopic expression of NNMT in SH-SY5Y human neuroblastoma cells increased adenosine triphosphate synthesis and complex I activity, effects of which were replicated by the addition of MeN. In this study, we investigated whether NNMT expression in SH-SY5Y conferred protection against mitotoxicity induced by rotenone, potassium cyanide (KCN), 2,4-dinitrophenol, and 6-hydroxydopamine, and whether any effects observed were mediated via increased MeN production. NNMT expression abolished the toxic effects of KCN, 2,4-dinitrophenol, and 6-hydroxydopamine, and reduced that of rotenone. In contrast, although MeN significantly reduced the toxicity of rotenone, it had no effect upon the toxicity of KCN, 2,4-dinitrophenol, and 6-hydroxydopamine. These data show that NNMT is cytoprotective against toxins that inhibit various aspects of mitochondrial function, and that these are not mediated solely via increased MeN production, but in combination with other unidentified mechanisms. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:451-456, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21508