Document Detail

Toxic effects of nicotinamide methylation on mouse brain striatum neuronal cells and its relation to manganese.
MedLine Citation:
PMID:  22249857     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: It is well known that manganese (Mn) exposure is involved in parkinsonism. The aim of our study was to test the hypotheses that Mn affects nicotinamide N-methyltransferase (NNMT) activity, increases the metabolism of nicotinamide (NA) to 1-methylnicotinamide (MNA), and leads to neurocytotoxicity.
METHODS: Following demonstration of the effects of Mn concentrations on the survival rate of Mouse CD1 brain striatum neuronal cells (MS cells), the effect of Mn on NNMT activity was investigated by comparing the difference in the amount of MNA produced after various Mn concentrations were added to mouse brain cytosol fractions as an enzyme solution. Toxicity induced by MNA and its precursor NA on MS cells was measured.
RESULTS: The survival rate of MS cells decreased significantly with increasing concentrations of Mn in the culture medium. With respect to the influence of Mn on NNMT activity, NNMT activity increased significantly at Mn concentrations of 1 μmol/mg protein. MNA and NA neurotoxicity were compared by comparing cell survival rate. Cell survival rate dropped significantly when the cells were cultivated with 10 mM of MNA. There was also a tendency for the survival rate to fall following the addition of 10 mM NA; however, the difference with the control was not significant.
CONCLUSIONS: Our study suggests the possibility that Mn causes increased NNMT activity, thereby increasing MNA levels in the brain and bringing about neuron death. Daily absorption of Mn and NA may thus contribute to idiopathic Parkinson's disease.
Yayoi Mori; Akiko Sugawara; Masayoshi Tsuji; Takeyasu Kakamu; Satoshi Tsuboi; Hideyuki Kanda; Takehito Hayakawa; Tetsuhito Fukushima
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-15
Journal Detail:
Title:  Environmental health and preventive medicine     Volume:  17     ISSN:  1347-4715     ISO Abbreviation:  Environ Health Prev Med     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-10     Completed Date:  2013-01-23     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  9609642     Medline TA:  Environ Health Prev Med     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  371-6     Citation Subset:  IM    
Department of Hygiene and Preventive Medicine, Fukushima Medical University School of Medicine, Japan.
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MeSH Terms
Cell Survival / drug effects
Dithiothreitol / toxicity*
Manganese / toxicity*
Neostriatum / drug effects*,  metabolism
Niacinamide / analogs & derivatives*,  metabolism*
Nicotinamide N-Methyltransferase / metabolism
Reg. No./Substance:
3106-60-3/N(1)-methylnicotinamide; 3483-12-3/Dithiothreitol; 7439-96-5/Manganese; 98-92-0/Niacinamide; EC N-Methyltransferase

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