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在皮质细胞培养物中,含有钙结合蛋白D28K的神经元,而非表达热休克蛋白70(HSP70)的神经元,对HIV-1包膜(gp120)毒性更具抗性。

Calbindin D28K-containing neurons, and not HSP70-expressing neurons, are more resistant to HIV-1 envelope (gp120) toxicity in cortical cell cultures.

作者信息

Diop A G, Lesort M, Esclaire F, Dumas M, Hugon J

机构信息

Cellular Neurobiology Unit-Laboratory of Histology, Medical Institute of Cellular and Molecular Biology, Faculty of Medicine, Limoges, France.

出版信息

J Neurosci Res. 1995 Oct 1;42(2):252-8. doi: 10.1002/jnr.490420213.

DOI:10.1002/jnr.490420213
PMID:8568926
Abstract

HIV-1-associated cognitive/motor complex is one of the major neurological complications of AIDS and is associated with neuronal loss. Gp120, the HIV envelope protein, is toxic for neurons in cultures and produces a rise in intracytosolic calcium. This neurotoxicity is dose-dependent and time-dependent. We evaluated the selective gp120 toxicity in primary neuronal cultures for calbindin-free and calbindin-containing neurons with semi-quantitative immunocytochemistry using an anti-calbindin D28K monoclonal antibody. The number of immunolabelled neurons was inversely correlated to neuronal survival. In cultures exposed to gp120 (100 pM) for 24 hr the neuronal survival of initial platings was 19.7 +/- 2.1% and the percentage of neuronal survival was 84.6 +/- 4.9% in control cultures exposed to the vehicle. The corresponding percentages of immunolabelled neurons were 85.0 +/- 2.1% in treated cultures and 23.6 +/- 3.1% in control cultures (P < 0.001). The expression of heat shock proteins by heating cell cultures did not protect neurons from gp120 toxicity. These results suggest that calbindin D2K28-containing neurons are more resistant to gp120-toxicity in this cell culture system.

摘要

HIV-1相关的认知/运动复合体是艾滋病主要的神经并发症之一,与神经元丧失有关。HIV包膜蛋白Gp120对培养中的神经元有毒性,可使胞内钙升高。这种神经毒性呈剂量和时间依赖性。我们使用抗钙结合蛋白D28K单克隆抗体,通过半定量免疫细胞化学方法,评估了原代神经元培养物中Gp120对无钙结合蛋白和含钙结合蛋白神经元的选择性毒性。免疫标记神经元的数量与神经元存活率呈负相关。在暴露于Gp120(100 pM)24小时的培养物中,初始接种的神经元存活率为19.7±2.1%,而在暴露于赋形剂的对照培养物中,神经元存活率为84.6±4.9%。处理过的培养物中免疫标记神经元的相应百分比为85.0±2.1%,对照培养物中为23.6±3.1%(P<0.001)。通过加热细胞培养物来表达热休克蛋白并不能保护神经元免受Gp120毒性。这些结果表明,在该细胞培养系统中,含钙结合蛋白D2K28的神经元对Gp120毒性更具抗性。

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