Toxic effects of nicotinamide methylation on mouse brain striatum neuronal cells and its relation to manganese

Yayoi Mori, Akiko Sugawara, Masayoshi Tsuji, Takeyasu Kakamu, Satoshi Tsuboi, Hideyuki Kanda, Takehito Hayakawa, Tetsuhito Fukushima

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 lmol/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.

Original languageEnglish
Pages (from-to)371-376
Number of pages6
JournalEnvironmental Health and Preventive Medicine
Volume17
Issue number5
DOIs
Publication statusPublished - Sep 1 2012
Externally publishedYes

Fingerprint

Niacinamide
Poisons
Manganese
Methylation
Nicotinamide N-Methyltransferase
Brain
Cell Survival
Parkinsonian Disorders
Cytosol
Parkinson Disease
Culture Media
N(1)-methylnicotinamide
Neurons

Keywords

  • Cytotoxicity
  • Manganese
  • Mouse CD1 brain striatum neuronal cells
  • Nicotinamide N-methyltransferase
  • Parkinson's disease

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health

Cite this

Toxic effects of nicotinamide methylation on mouse brain striatum neuronal cells and its relation to manganese. / Mori, Yayoi; Sugawara, Akiko; Tsuji, Masayoshi; Kakamu, Takeyasu; Tsuboi, Satoshi; Kanda, Hideyuki; Hayakawa, Takehito; Fukushima, Tetsuhito.

In: Environmental Health and Preventive Medicine, Vol. 17, No. 5, 01.09.2012, p. 371-376.

Research output: Contribution to journalArticle

Mori, Yayoi ; Sugawara, Akiko ; Tsuji, Masayoshi ; Kakamu, Takeyasu ; Tsuboi, Satoshi ; Kanda, Hideyuki ; Hayakawa, Takehito ; Fukushima, Tetsuhito. / Toxic effects of nicotinamide methylation on mouse brain striatum neuronal cells and its relation to manganese. In: Environmental Health and Preventive Medicine. 2012 ; Vol. 17, No. 5. pp. 371-376.
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AB - 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 lmol/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.

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