Parkinson's disease (PD) is a neurodegenerative disorder resulting from mitochondrial dysfunction in dopaminergic neurons. Mitochondria are believed to be responsible for cellular Mg2+ homeostasis. Mg2+ is indispensable for maintaining ordinal cellular functions, hence perturbation of the cellular Mg2+ homeostasis may be responsible for the disorders of physiological functions and diseases including PD. However, the changes in intracellular Mg2+ concentration ([Mg2+]i) and the role of Mg2+ in PD have still been obscure. In this study, we investigated [Mg2+]i and its effect on neurodegeneration in the 1-methyl-4-phenylpyridinium (MPP+) model of PD in differentiated PC12 cells. Application of MPP+ induced an increase in [Mg2+]i immediately via two different pathways: Mg2+ release from mitochondria and Mg2+ influx across cell membrane, and the increased [Mg2+]i sustained for more than 16h after MPP+ application. Suppression of Mg2+ influx decreased the viability of the cells exposed to MPP+. The cell viability correlated highly with [Mg2+]i. In the PC12 cells with suppressed Mg2+ influx, ATP concentration decreased and the amount of reactive oxygen species (ROS) increased after an 8h exposure to MPP+. Our results indicate that the increase in [Mg2+]i inhibited cellular ROS generation and maintained ATP production, which resulted in the protection from MPP+ toxicity.
|ジャーナル||Biochimica et Biophysica Acta - Molecular Cell Research|
|出版ステータス||Published - 2015 12月 1|
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