Qu Xiaoling, Qi Yipeng, Lan Ping, Li Qilan
Institute of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, PR China.
FEBS Lett. 2002 Oct 9;529(2-3):325-31. doi: 10.1016/s0014-5793(02)03350-1.
HAP, a novel human apoptosis-inducing protein, was identified to localize exclusively to the endoplasmic reticulum (ER) in our previous work. In the present work, we reported that ectopic overexpression of HAP proteins caused the rapid and sustained elevation of the intracellular cytosolic Ca(2+), which originated from the reversible ER Ca(2+) stores release and the extracellular Ca(2+) influx. The HeLa cells apoptosis induced by HAP proteins was not prevented by establishing the clamped cytosolic Ca(2+) condition, or by buffering of the extracellular Ca(2+) with EGTA, suggesting that the depletion of ER Ca(2+) stores rather than the elevation of cytosolic Ca(2+) or the extracellular Ca(2+) entry contributed to HAP-induced HeLa cells apoptosis. Caspase-3 was also activated in the process of HAP-triggered apoptotic cell death.
HAP是一种新型的人类凋亡诱导蛋白，在我们之前的研究中被确定仅定位于内质网（ER）。在本研究中，我们报告称HAP蛋白的异位过表达导致细胞内胞质Ca(2+)迅速且持续升高，这源于内质网Ca(2+)储存的可逆性释放以及细胞外Ca(2+)内流。通过建立钳制的胞质Ca(2+)条件，或用EGTA缓冲细胞外Ca(2+)，并不能阻止HAP蛋白诱导的HeLa细胞凋亡，这表明内质网Ca(2+)储存的耗竭而非胞质Ca(2+)的升高或细胞外Ca(2+)的内流导致了HAP诱导的HeLa细胞凋亡。在HAP触发的凋亡细胞死亡过程中，半胱天冬酶-3也被激活。
