Oncotarget

Research Papers:

Isradipine attenuates MPTP-induced dopamine neuron degeneration by inhibiting up-regulation of L-type calcium channels and iron accumulation in the substantia nigra of mice

Qi-Min Wang, Yu-Yu Xu, Shang Liu and Ze-Gang Ma _

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Oncotarget. 2017; 8:47284-47295. https://doi.org/10.18632/oncotarget.17618

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Abstract

Qi-Min Wang1, Yu-Yu Xu1, Shang Liu1 and Ze-Gang Ma1,2

1Department of Physiology, School of Basic Medicine, Medical College of Qingdao University, Qingdao, China

2Institute of Brain Science and Disorders, Qingdao University, Qingdao, China

Correspondence to:

Ze-Gang Ma, email: mazegang2000@163.com

Keywords: L-type calcium channel, isradipine, dopamine neuron, iron accumulation, Parkinson’s disease

Received: March 13, 2017     Accepted: April 12, 2017     Published: May 04, 2017

ABSTRACT

The aim of this study is to investigate the effects of L-type calcium channels (LTCCs) on MPTP-induced dopamine (DA) neuron degeneration and iron accumulation in the substantia nigra (SN) of mice. By real-time PCR and western blots, we first quatified expressions of L-type Cav1.2 and Cav1.3 calcium channel α1 subunits in the SN of experimental mice treated with MPTP. We found that the expressions of Cav1.2 and Cav1.3 calcium channel α1 subunits markedly increased after MPTP treatment for 2 and 3 weeks. Secondly, we observed the effects of isradipine, a LTCC antagonist, on MPTP-induced DA neuron degeneration and iron accumulation in the SN. Our results showed that isradipine treatment prevented against MPTP-induced Cav1.2 and Cav1.3 calcium channel α1 subunits up-regulation in the SN. We also found that isradipine prevented against MPTP-induced DA neuron depletion in the SN and partly restored the DA content in the striatum. Moreover, we found that isradipine inhibited the increase of iron positive cells in the SN of the MPTP-treated mice. Finally, we investigated the effects of isradipine on cellular iron accumulation in the dopaminergic MES23.5 cell line. Our studies showed that MPP+ treatment accelerated iron influx in the MES23.5 cells. Treatment with Bayk8644 further aggravated iron accumulation. Treatment with isradipine prevented against MPP+-induced iron influx in the MES23.5 cells. These results suggest that up-regulation of LTCCs may be responsible for the DA neuron degeneration in the MPTP-treated mice, The LTCCs may directly contribute to iron influx into DA neurons, and isradipine may suppress cellular iron accumulation and prevents neurodegeneration.


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