Heat shock inhibits hydrogen peroxide-induced apoptosis in cultured astrocytes
Heat shock inhibits hydrogen peroxide-induced apoptosis in cultured astrocytes
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DOI：
10.1016/s0006-8993(02)02888-3
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发表时间：
2002-08-16
期刊：
影响因子：
2.9
通讯作者：
Matsuda, T
中科院分区：
文献类型：
--
作者：
Takuma, K;Mori, K;Matsuda, T
热休克蛋白（HSP）已被证明可以作为细胞凋亡抑制剂，但这种抗细胞凋亡作用在中枢神经系统中尚不清楚。先前的热休克已被证明可以在再灌注损伤模型中保护星形胶质细胞免于细胞死亡（Brain Res.735（1996）265）。本研究探讨了热休克保护作用的机制。星形胶质细胞在 40°C 下预孵育 10 分钟可减弱过氧化氢 (H2O2) 引起的细胞活力下降、DNA 梯形成和核浓缩，而这些影响可被蛋白质合成抑制剂放线菌酮阻断。热应激抑制H2O2诱导的caspase-3样蛋白酶活性增加，但不影响H2O2诱导的线粒体膜电位损失。由预热细胞制备的胞质溶胶不影响 Ca2+ 诱导的线粒体肿胀（可渗透过渡孔的标志物）。热应激对 H2O2 诱导的细胞活力下降的保护作用不受丝裂原激活蛋白/细胞外信号调节激酶激酶抑制剂 2'-氨基-3'-甲氧基黄酮、磷脂酰肌醇-3 激酶抑制剂渥曼青霉素和 NF-κB 抑制剂的影响 吡咯烷二硫代氨基甲酸酯。这些发现表明，HSP 通过抑制 caspase-3 激活来抑制细胞凋亡，而不影响线粒体功能障碍。 (C) 2002 Elsevier Science B.V. 保留所有权利。
Heat shock proteins (HSPs) have been shown to act as inhibitors of apoptosis, but this anti-apoptotic effect is not known in the central nervous system. Prior heat shock has been demonstrated to protect astrocytes from cell death in a model of reperfusion injury (Brain Res. 735 (1996) 265). The present study examines the mechanism underlying the protective effect of the heat shock. Preincubation of astrocytes at 40 degreesC for 10 min attenuated the hydrogen peroxide (H2O2)-induced decrease in cell viability, DNA ladder formation and nuclear condensation, and these effects were blocked by the protein synthesis inhibitor cycloheximide. The thermal stress inhibited the H2O2-induced increase in caspase-3 like protease activity, but it did not affect the H2O2-induced loss of mitochondrial membrane potential. The cytosol prepared from preheated cells did not affect Ca2+-induced swelling of mitochondria, a marker of the permeable transition pore. The protective effect of the thermal stress on the H2O2-induced decrease in cell viability was not affected by the mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor 2'-amino-3'-methoxyflavone, the phosphatidylinositol-3 kinase inhibitor wortmannin and the NF-kappaB inhibitor pyrrolidinedithiocarbamate. These findings suggest that HSPs inhibit apoptosis via an inhibition of caspase-3 activation without effect on mitochondrial dysfunction. (C) 2002 Elsevier Science B.V. All rights reserved.