RRC ID 61736
Author Shindo Y, Yamanaka R, Suzuki K, Hotta K, Oka K.
Title Intracellular magnesium level determines cell viability in the MPP(+) model of Parkinson's disease.
Journal Biochim Biophys Acta
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 the increase in [Mg²⁺]i inhibited cellular ROS generation and maintained ATP production, which resulted in the protection from MPP⁺ toxicity.
Volume 1853(12)
Pages 3182-91
Published 2015-12-1
DOI 10.1016/j.bbamcr.2015.08.013
PII S0167-4889(15)00282-7
PMID 26319097
MeSH 1-Methyl-4-phenylpyridinium / toxicity* Adenosine Triphosphate / metabolism Animals Disease Models, Animal* Dose-Response Relationship, Drug Magnesium / metabolism* PC12 Cells Parkinson Disease / metabolism* Rats
IF 3.411
Human and Animal Cells PC-12(RCB0009)