Isradipine Can Alleviate Iron-Induced Toxicity caused by Elevated Intracellular Calcium in MES23.5 Cell

Isradipine Can Alleviate Iron-Induced Toxicity caused by Elevated Intracellular Calcium in MES23.5 Cell

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Author(s)

Author(s): Wan Wen-Ping

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DOI: 10.18483/ijSci.1893 13 48 90-96 Volume 8 - Jan 2019

Abstract

Previous research demonstrated that the progressive accumulation of iron in the substantia nigra pars compacta (SNpc) may contribute to dopaminergic (DA) neurons selective degeneration in Parkinson's disease (PD). However, the etiology and mechanism underlying iron-induced neurotoxicity processes are as yet unresolved. It has been reported that L-type calcium channels (LTCCs) may mediate iron influx into neuronal cells and can compete with calcium for common routes to enter primary neurons. The present study, we found that isradipine can alleviate iron-induced toxicity caused by raising intracellular calcium in MES23.5 cells. Analysis of experimental results revealed that an increase in extracellular free CaCl2 (500 µmol/L) is sufficient to promote FeSO4 (100 µmol/L) entry by activating L-type Ca2+ channels (LTCCs) significantly. The enhancement of calcium and/or iron influx was accompanied by a corresponding decrease of cell viability and higher susceptibility of toxicity, such as decrease of mitochondrial membrane potential (ΔΨm) and increase of nucleus pyknosis ratio and cleaved caspase-3 protein expression in MPP+ (5 µmol/L) treatment MES23.5 cells. Pre-treatment with isradipine (10 µmol/L), a LTCCs blocker, for 15 min, can antagonize calcium and/or iron-induced neurotoxicity. These results suggest that application of isradipine may be a potential method for the treatment of the neurodegenerative disease induced by calcium and/or iron dysmetabolism.

Keywords

Iron, Mitochondria, Neurotoxicity, L-Type Ca2+ Channel

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International Journal of Sciences is Open Access Journal.
This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License.
Author(s) retain the copyrights of this article, though, publication rights are with Alkhaer Publications.

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