HIV-1 COAT PROTEIN NEUROTOXICITY PREVENTED BY CALCIUM-CHANNEL ANTAGONISTS
HIV-1 COAT PROTEIN NEUROTOXICITY PREVENTED BY CALCIUM-CHANNEL ANTAGONISTS
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DOI：
10.1126/science.2326646
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发表时间：
1990-04-20
期刊：
影响因子：
56.9
通讯作者：
LIPTON, SA
中科院分区：
文献类型：
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作者：
DREYER, EB;KAISER, PK;LIPTON, SA
来自人类免疫缺陷病毒 1 型 (HIV-1) 的外壳蛋白 gp120 增加细胞内游离钙，并损伤培养物中的啮齿动物视网膜神经节细胞和海马神经元。高度纯化的重组 gp120 包膜蛋白在皮摩尔浓度下以剂量依赖性方式产生这些效应。使用 gp120 抗体进行免疫沉淀，但不使用含免疫球蛋白的对照血清进行免疫沉淀，耗尽了病毒包膜蛋白的溶液，并且还防止了细胞内钙的升高和神经元毒性。通过暂时降低细胞外钙或添加二氢吡啶钙通道拮抗剂尼莫地平 (100 nM) 可以消除 gp120 诱导的细胞内钙增加。钙通道拮抗剂还可以预防 gp120 诱导的神经元损伤。此外，细胞内储存似乎对 gp120 引起的钙增加有很大贡献。由于细胞内钙的增加与神经毒性有关，因此 gp120 对神经元的损伤作用可能与这种机制有关，并且钙通道拮抗剂的治疗可能有助于减轻 HIV-1 相关的神经元损伤。
Coat protein gp120 from the human immunodeficiency virus type-1 (HIV-1) increased intracellular free calcium and injured rodent retinal ganglion cells and hippocampal neurons in culture. Highly purified recombinant gp120 envelope protein produced these effects in a dose-dependent fashion at picomolar concentrations. Immunoprecipitation with antibody to gp120, but not with control immunoglobulin-containing serum, depleted solutions of the viral envelope protein and also prevented both the rise in intracellular calcium and neuronal toxicity. The gp120-induced increase in intracellular calcium was abrogated by transiently lowering extracellular calcium or by adding the dihydropyridine calcium channel antagonist nimodipine (100 nM). Calcium channel antagonists also prevented gp120-induced neuronal injury. In addition, intracellular stores appeared to contribute substantially to the increase in calcium elicited by gp120. Since increases in intracellular calcium have been associated with neurotoxicity, it is possible that an injurious effect of gp120 on neurons might be related to this mechanism and that treatment with calcium channel antagonists may prove useful in mitigating HIV-1-related neuronal injury.