Laboratory of Clinical and Experimental Neuroscience, Division of Cell Biology and Physiology, CSIR-Indian Institute of Chemical Biology, Kolkata, 4, Raja Subodh Mullick Road, Jadavpur, 700032, India.
Laboratory of Clinical and Experimental Neuroscience, Division of Cell Biology and Physiology, CSIR-Indian Institute of Chemical Biology, Kolkata, 4, Raja Subodh Mullick Road, Jadavpur, 700032, India; Inter University Centre for Biomedical Research & Super Speciality Hospital, Mahatma Gandhi University Campus at Thalappady, Rubber Board P.O., Kottayam, Kerala, 686009, India.
J Chem Neuroanat. 2019 Jan;95:89-94. doi: 10.1016/j.jchemneu.2018.02.001. Epub 2018 Feb 7.
We have recently demonstrated neuroprotective abilities of nimodipine, an L-type voltage dependent calcium channel (VDCC) blocker in cellular and animal models of Parkinson's disease (PD). To understand the calcium regulatory mechanisms in the disease pathogenesis, the present study examined calcium regulatory proteins calbindin and calpain mRNA and protein levels employing quantitative PCR and western blot in 1-methyl-4-phenyl pyridinium ion (MPP)-treated SH-SY5Y cell lines and in the striatum of mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). mRNA and protein levels of calbindin were lower, while that of calpain were higher in MPP-treated SH-SY5Y cells and MPTP-treated mouse striatum as compared to their respective controls. Nimodipine pretreatment significantly attenuated these effects in the parkinsonian neurotoxin-treated SH-SY5Y cell line and in the mouse striatum. The activities of the apoptotic mediator, caspase-3 and calpain were increased in the neurotoxin-treated groups as compared to their respective controls, which was ameliorated by nimodipine pretreatment. These results suggest that parkinsonian neurotoxin-mediated dopaminergic neuronal death might involve defects in calcium regulatory proteins that control intracellular calcium homeostasis, and these could be corrected by inhibiting L-type VDCC activity. These findings support the notion that hypertensive patients who are on long-term intake of dihydropyridine have reduced risk for PD.
我们最近在帕金森病（PD）的细胞和动物模型中证明了尼莫地平（一种 L 型电压依赖性钙通道（VDCC）阻滞剂）的神经保护作用。为了了解疾病发病机制中的钙调节机制，本研究采用定量 PCR 和 Western blot 检测了 1-甲基-4-苯基吡啶离子（MPP）处理的 SH-SY5Y 细胞系和 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的小鼠纹状体中的钙调节蛋白钙结合蛋白和钙蛋白酶 mRNA 和蛋白水平。与各自的对照相比，MPP 处理的 SH-SY5Y 细胞和 MPTP 处理的小鼠纹状体中的钙结合蛋白 mRNA 和蛋白水平较低，而钙蛋白酶的 mRNA 和蛋白水平较高。尼莫地平预处理可显著减轻帕金森神经毒素处理的 SH-SY5Y 细胞系和小鼠纹状体中的这些作用。与各自的对照相比，神经毒素处理组中的凋亡介质 caspase-3 和钙蛋白酶的活性增加，尼莫地平预处理可改善这种情况。这些结果表明，帕金森神经毒素介导的多巴胺能神经元死亡可能涉及控制细胞内钙稳态的钙调节蛋白的缺陷，而抑制 L 型 VDCC 活性可以纠正这些缺陷。这些发现支持这样一种观点，即长期服用二氢吡啶的高血压患者患 PD 的风险降低。
