RRC ID |
61736
|
著者 |
Shindo Y, Yamanaka R, Suzuki K, Hotta K, Oka K.
|
タイトル |
Intracellular magnesium level determines cell viability in the MPP(+) model of Parkinson's disease.
|
ジャーナル |
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.
|
巻・号 |
1853(12)
|
ページ |
3182-91
|
公開日 |
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
|
リソース情報 |
ヒト・動物細胞 |
PC-12(RCB0009) |