Intracellular magnesium level determines cell viability in the MPP(+) model of Parkinson's disease

Biochimica Et Biophysica Acta
Yutaka ShindoKotaro Oka

Abstract

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 16 h 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 th...Continue Reading

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Citations

May 28, 2020·International Journal of Molecular Sciences·Mark F McCarty, Aaron Lerner
Jul 25, 2019·International Journal of Molecular Sciences·Ryu YamanakaKotaro Oka
Sep 8, 2019·Cell Calcium·Valentina Trapani, Federica I Wolf
Jul 25, 2021·International Journal of Molecular Sciences·Xuan WangJunjie Luo

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