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

Yutaka Shindo, Ryu Yamanaka, Koji Suzuki, Kohji Hotta, Kotaro Oka

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)3182-3191
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1853
Issue number12
DOIs
Publication statusPublished - 2015 Dec 1

Keywords

  • ATP
  • Magnesium
  • Mitochondria
  • Neuroprotection
  • Parkinson's disease
  • Reactive oxygen species

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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