Toxic effects of nicotinamide methylation on mouse brain striatum neuronal cells and its relation to manganese
Toxic effects of nicotinamide methylation on mouse brain striatum neuronal cells and its relation to manganese
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DOI：
10.1007/s12199-011-0262-6
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发表时间：
2012-09-01
影响因子：
4.7
通讯作者：
Fukushima, Tetsuhito
中科院分区：
文献类型：
--
作者：
Mori, Yayoi;Sugawara, Akiko;Fukushima, Tetsuhito
众所周知，锰（Mn）暴露与帕金森病有关。本研究的目的是验证锰影响烟酰胺N-甲基转移酶（NNMT）活性、促进烟酰胺（NA）代谢为1-甲基烟酰胺（MNA）并导致神经细胞毒性的假设。（MS细胞），通过比较在将不同Mn浓度作为酶溶液添加到小鼠脑胞质溶胶级分中后产生的MNA的量的差异来研究Mn对NNMT活性的影响。测定了MNA及其前体NA对MS细胞的毒性作用，结果表明，随着培养基中Mn浓度的增加，MS细胞的存活率明显下降。关于锰对NNMT活性的影响，NNMT活性在锰浓度为1 μ mol/mg蛋白质时显著增加。通过比较细胞存活率比较MNA和NA的神经毒性。当用10 mM MNA培养细胞时，细胞存活率显著下降。也有一种趋势，生存率下降后，加入10 mM NA，然而，与对照组的差异是不显着的，我们的研究表明，锰的可能性，导致增加NNMT活性，从而增加MNA水平在大脑中，并带来神经元死亡。因此，每日吸收锰和NA可能有助于特发性帕金森病。
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.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.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 mu mol/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.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.