Changes in cytosolic Ca2+ levels regulate Bcl-xS and Bcl-xL expression in spermatogenic cells during apoptotic death
Changes in cytosolic Ca2+ levels regulate Bcl-xS and Bcl-xL expression in spermatogenic cells during apoptotic death
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DOI：
10.1074/jbc.m508648200
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发表时间：
2006-01-27
影响因子：
4.8
通讯作者：
Shaha, C
中科院分区：
文献类型：
--
作者：
Mishra, DP;Pal, R;Shaha, C
Bclx以两种亚型存在，即抗凋亡型Bclxl和促凋亡率Bclxs。这两种形式之间的关键平衡似乎对细胞生存很重要；然而，仍然不清楚生命平衡是如何维持的。本研究利用体外生精细胞凋亡模型，对钙离子在调控细胞凋亡过程中可能起的作用提供了新的认识。2，5-己二酮是常见工业溶剂正己烷的代谢物，它通过T型钙通道引起细胞内氧自由基的显著增加和细胞内钙离子的增加。由于上述变化，Bclxs的表达增加，同时Bclxl的表达下降，从而改变了两种蛋白的比例。用T型钙通道阻断剂匹莫齐特阻断钙离子内流，可使Bclxs减少，Bclxl表达增加。这导致防止线粒体电位丧失，降低caspase-3活性，抑制DNA片段化，并提高细胞存活率。另一种选择是，钙离子载体导致了编码Bclxs的亚型比编码Bclxl的异构体增加。因此，本研究提出了钙离子在调控Bclxs和Bclxl表达，最终调节细胞命运中的作用。
Bcl-x exists in two isoforms, the anti-apoptotic form Bcl-xL and the proapoptotic form Bcl-xS. The critical balance between the two forms appears to be important for cell survival; however, it is still not clear exactly how the vital balance is maintained. Using an in vitro spermatogenic cell apoptosis model, this study provides a new insight into the possible role of Ca2+ in regulating the Bcl-xS and Bcl-xL expression. 2,5-Hexanedione, a metabolite of the common industrial solvent n-hexane, caused a significant increase in reactive oxygen species followed by an enhancement of intracellular Ca2+ through the T-type Ca2+ channels. Consequent to the above changes, expression of Bcl-xS increased with a concomitant drop in Bcl-xL expression, thus altering the ratio of the two proteins. Impediment of Ca2+ influx by using a T-type Ca2+ channel blocker pimozide resulted in a decrease in Bcl-xS and an increase in Bcl-xL expression. This caused prevention of mitochondrial potential loss, reduction of caspase-3 activity, inhibition of DNA fragmentation, and increase in cell survival. Alternatively, Ca2+ ionophores caused an increase of Bcl-xS encoding isoform over the Bcl-xL-encoding isoform. Therefore, this study proposes a role for Ca2+ in regulation of Bcl-xS and Bcl-xL expression and ultimately cell fate.