In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance
In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance
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DOI：
10.1016/s0006-8993(01)02774-3
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发表时间：
2001-09-28
期刊：
影响因子：
2.9
通讯作者：
Margulis, B
中科院分区：
文献类型：
--
作者：
Guzhova, I;Kislyakova, K;Margulis, B
神经胶质细胞释放多种支持神经元功能的分子。由于热壳蛋白（Hsps）是重要的神经元的生存代谢应激，神经胶质细胞可以释放的诱导形式的70 kDa的lisp（Hsp 70）的可能性进行了检查。此外，通过摄取加入细胞外液中的组成型和诱导型Hsp 70（Hsc/Hsp 70）的混合物，测试神经元细胞显示增加的应激耐受性的能力。使用人T98 G神经胶质瘤细胞和分化的LA-N-5神经母细胞瘤细胞作为模型胶质细胞和神经元来研究这些点。Hsp 70用亲和层析、Western印迹和免疫荧光显微镜进行分析。无论是在正常条件下还是在热休克条件下，胶质瘤细胞都能将Hsp 70输出到培养基中。神经胶质Hsp 70的释放量范围为每天每10（6）个细胞5至15 pg，在热休克后更大。神经母细胞瘤细胞在生物素化的Hsc/Hsp 70加入到培养基后1小时内吸收了它，这使它们对热休克（44 ℃）和星形孢菌素诱导的凋亡更具抵抗力。这种应激耐受性的增强对于用佛波酯诱导分化的神经母细胞瘤细胞尤其重要，因为这些“成熟神经元”显示出内源性Hsp 70下降10倍，同时伴有对热休克和星形孢菌素诱导的细胞凋亡的易感性增加。这些结果表明，细胞外热休克蛋白70可能提供了一种手段，胶质细胞可以影响神经元的功能，也许提高神经元的应激耐受性。(C)2001 Elsevier Science BY保留所有权利。
Glial cells release a variety of molecules that support neuronal function. Because heat shuck proteins (Hsps) are important in the survival of neurons subjected to metabolic stress, the possibility that glia can release the inducible form of the 70 kDa lisp (Hsp70) was examined. Additionally, the ability of neuronal cells to show increased stress tolerance by taking up a mixture of constitutive and inducible forms of Hsp70 (Hsc/Hsp70) added to the extracellular fluid was tested, Human T98G glioma cells and differentiated LA-N-5 neuroblastoma cells were used as model glia and neurons to investigate these points. Hsp70 was analyzed using affinity chromatography, Western blotting, and immunofluorescence microscopy. The glioma cells were shown to export Hsp70 into the culture medium whether under normal conditions or subjected to heat shock. The amount of glial Hsp70 released ranged from 5 to 15 pg per 10(6) cells per day, being greater following heat shock. Neuroblastoma cells took up biotinylated Hsc/Hsp70 within I h after it was added to the culture medium and it made them more resistant to heat shock (44 degreesC) and to staurosporine-induced apoptosis. This increased stress tolerance was especially important in neuroblastoma cells induced to differentiate with phorbol ester because those 'mature neurons' showed a 10-fold decline in endogenous Hsp70, which was accompanied by increased susceptibility to heat shock and staurosporine-induced apoptosis. These results suggest that extracellular Hsp70 may provide a means by which glia can affect neuronal function, perhaps enhancing neuronal stress tolerance. (C) 2001 Elsevier Science BY All rights reserved.