Key apoptotic pathways for heat-induced programmed germ cell death in the testis
Key apoptotic pathways for heat-induced programmed germ cell death in the testis
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DOI：
10.1210/en.2003-0175
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发表时间：
2003-07-01
期刊：
影响因子：
4.8
通讯作者：
Swerdloff, RS
中科院分区：
文献类型：
--
作者：
Hikim, APS;Lue, YH;Swerdloff, RS
将大鼠睾丸短期暴露于温和的热量下（43°C，15 分钟）会在 6 小时内导致生殖细胞凋亡的阶段和细胞特异性激活。在热敏感生殖细胞中，Bax 从细胞质重新分布到核旁定位，从而引发细胞凋亡。在这里，我们发现 Bax 的重新定位伴随着细胞色素 c 的胞质易位，并与起始 caspase 9 和刽子 caspase 3、6 和 7 的激活以及聚 (ADP) 核糖聚合酶的裂解相关。此外，通过对分级睾丸裂解物进行蛋白质印迹分析评估，在细胞凋亡早期，大量 Bax 也在内质网中积累。在使用 FasL 缺陷性 gld 小鼠的其他研究中，我们发现热诱导的生殖细胞凋亡并未被阻断，从而提供了证据表明 Fas 信号系统对于睾丸中热诱导的生殖细胞凋亡可能是可有可无的。综上所述，这些结果表明，线粒体依赖性途径以及可能还有内质网依赖性途径是睾丸中热诱导生殖细胞死亡的关键凋亡途径。
Short-term exposure ( 43 C for 15 min) of the rat testis to mild heat results within 6 h in stage- and cell-specific activation of germ cell apoptosis. Initiation of apoptosis was preceded by a redistribution of Bax from a cytoplasmic to paranuclear localization in heat-susceptible germ cells. Here we show that the relocation of Bax is accompanied by cytosolic translocation of cytochrome c and is associated with activation of the initiator caspase 9 and the executioner caspases 3, 6, and 7 and cleavage of poly( ADP) ribose polymerase. Furthermore, early in apoptosis, a significant amount of Bax also accumulates in endoplasmic reticulum, as assessed by Western blot analyses of fractionated testicular lysates. In additional studies using the FasL-defective gld mice, we have shown that heat-induced germ cell apoptosis is not blocked, thus providing evidence that the Fas signaling system may be dispensable for heat-induced germ cell apoptosis in the testis. Taken together, these results demonstrate that the mitochondria- and possibly also endoplasmic reticulum-dependent pathways are the key apoptotic pathways for heat-induced germ cell death in the testis.