载脂蛋白E异构体通过ω-芋螺毒素IVa敏感的钙通道差异性地增加细胞内钙离子浓度。
Apolipoprotein E isoforms increase intracellular Ca2+ differentially through a omega-agatoxin IVa-sensitive Ca2+-channel.
作者信息
Müller W, Meske V, Berlin K, Scharnagl H, März W, Ohm T G
机构信息
Institut für Physiologie der Charité, Berlin, Germany.
出版信息
Brain Pathol. 1998 Oct;8(4):641-53. doi: 10.1111/j.1750-3639.1998.tb00190.x.
Abstract
Apolipoprotein E (apoE) is the major apolipoprotein in the brain and is known for its important role in plasticity and neurodegeneration. We show that apoE dose-dependently increases intracellular free Ca2+ in rat hippocampal astrocytes and neurons. This effect varies with isoforms in the order E4 > E3 > E2. It is insensitive to blockade of action potentials by tetrodotoxin or inhibition of binding of apoE by heparinase, by the LRP ligand lactoferrin and by low density lipoprotein. ApoE evoked Ca2+-increases are blocked in zero [Ca]o and by the Ca-channel antagonists nickel and omega-Agatoxin-IVa but not by nifedipine and omega-Conotoxin-GVIa, demonstrating an isoform-specific activation of P/Q type Ca2+-channels. This novel mechanism is discussed with respect to Alzheimer's disease, that is linked for most cases to the apoE epsilon-allelic variation (epsilon4 > epsilon3 > epsilon2).
摘要
载脂蛋白E（apoE）是大脑中的主要载脂蛋白，因其在可塑性和神经退行性变中的重要作用而闻名。我们发现，apoE能使大鼠海马星形胶质细胞和神经元内的细胞内游离Ca2+呈剂量依赖性增加。这种效应因亚型而异，顺序为E4 > E3 > E2。它对河豚毒素阻断动作电位或肝素酶、LRP配体乳铁蛋白以及低密度脂蛋白抑制apoE结合不敏感。在零[Ca]o环境中以及使用钙通道拮抗剂镍和ω-银环蛇毒素-IVa时，apoE引起的Ca2+增加被阻断，但硝苯地平和ω-芋螺毒素-GVIa则无此作用，这表明P/Q型钙通道存在亚型特异性激活。针对阿尔茨海默病讨论了这一新机制，在大多数情况下，阿尔茨海默病与apoE ε等位基因变异（ε4 > ε3 > ε2）有关。
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