Altered expression of Mg2+ transport proteins during Parkinson's disease-like dopaminergic cell degeneration in PC12 cells

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Mg2+ is an essential cation to maintain cellular functions, and intracellular Mg2+ concentration ([Mg2+]i) is regulated by Mg2+ channels and transporters. In our previous study, we demonstrated that MPP+ elicits Mg2+ influx across the cell membrane and Mg2+ mobilization from mitochondria, and the resulting [Mg2+]i is an important determinants of the cell viability in MPP+ model of Parkinson's disease (PD). It indicates that cellular Mg2+ transport is one of the important factors to determine the progress of PD. However, whether the expression levels of Mg2+ transport proteins change in the progress of PD has still been obscure. In this study, we estimated the mRNA expression levels of Mg2+ transport proteins upon the exposure to MPP+. In thirteen Mg2+ transport proteins examined, mRNA expression level of SLC41A2 was increased and that of ACDP2, NIPA1 and MMgT2 were decreased. Knockdown of SLC41A2, ACDP2 or NIPA1 accelerated the MPP+-induced cell degeneration, and overexpression attenuated it. The decrease in the mRNA expression levels of NIPA1 and MMgT2 were also elicited by rotenone, H2O2 and FCCP, indicating that mitochondrial dysfunction related to this down-regulation. The increase in that of SLC41A2 was induced by an uncoupler, FCCP, as well as MPP+, suggesting that it is an intrinsic protection mechanism against depolarized mitochondrial membrane potential and/or cellular ATP depletion. Our results shown here indicate that alteration of Mg2+ transport proteins is implicated in the MPP+ model of PD, and it affects cell degeneration.

Original languageEnglish
Pages (from-to)1979-1984
Number of pages6
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1863
Issue number8
DOIs
Publication statusPublished - 2016 Aug 1

Keywords

  • Magnesium
  • Mitochondrial dysfunction
  • MPP
  • Parkinson's disease
  • Real-time PCR

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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