RRC ID 64906
Author Shindo Y, Yamanaka R, Suzuki K, Hotta K, Oka K.
Title Altered expression of Mg(2+) transport proteins during Parkinson's disease-like dopaminergic cell degeneration in PC12 cells.
Journal Biochim Biophys Acta
Abstract Mg(2+) is an essential cation to maintain cellular functions, and intracellular Mg(2+) concentration ([Mg(2+)]i) is regulated by Mg(2+) channels and transporters. In our previous study, we demonstrated that MPP(+) elicits Mg(2+) influx across the cell membrane and Mg(2+) mobilization from mitochondria, and the resulting [Mg(2+)]i is an important determinants of the cell viability in MPP(+) model of Parkinson's disease (PD). It indicates that cellular Mg(2+) transport is one of the important factors to determine the progress of PD. However, whether the expression levels of Mg(2+) transport proteins change in the progress of PD has still been obscure. In this study, we estimated the mRNA expression levels of Mg(2+) transport proteins upon the exposure to MPP(+). In thirteen Mg(2+) 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 Mg(2+) transport proteins is implicated in the MPP(+) model of PD, and it affects cell degeneration.
Volume 1863(8)
Pages 1979-84
Published 2016-8-1
DOI 10.1016/j.bbamcr.2016.05.003
PII S0167-4889(16)30131-8
PMID 27157538
MeSH 1-Methyl-4-phenylpyridinium / pharmacology Adenosine Triphosphate / metabolism Animals Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / pharmacology Cation Transport Proteins / biosynthesis* Cation Transport Proteins / genetics Cell Differentiation / drug effects Hydrogen Peroxide / pharmacology Ion Transport / drug effects MPTP Poisoning Magnesium / metabolism* Membrane Potential, Mitochondrial / drug effects Membrane Potential, Mitochondrial / physiology Mitochondria / metabolism Nerve Degeneration Nerve Growth Factor / pharmacology PC12 Cells / drug effects* PC12 Cells / metabolism RNA Interference RNA, Messenger / biosynthesis RNA, Messenger / genetics RNA, Small Interfering / genetics Rats Rotenone / pharmacology
IF 3.411
Human and Animal Cells PC-12(RCB0009)