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

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.