近日，研究人员发现身体如何控制细胞死亡的一个新机制，这一发现有利于开发出潜在的新的治疗靶标。
近来，加的夫大学生物科学学院的一个研究小组发现高酒精摄入可诱发胰腺炎和胰腺癌的发生发展。现在一项新的发表在Current Biology杂志上的研究揭示了两个众所周知的分子对于胰腺炎症和癌症的作用机制。
Cardiff研究团队探究了蛋白Bcl-2，Bcl-2已知能够抑制体内所有组织类型的细胞程序化死亡。但这项新研究发现Bcl-2在某些情况下能够促进肿瘤的生长。
有关胰腺细胞的研究表明，去除Bcl-2能激活细胞膜上泵出钙分子的蛋白。Bcl-2较低水平的话，程序性细胞死亡的水平增加。但他们发现，缺乏Bcl-2能显著防止另一种更危险的细胞死亡形式——坏死。该研究小组发现Bcl-2增加对坏死的抑制直接与增加钙泵的活性有关。Oleg Gerasimenko博士和Ole Petersen教授率领的团队认为，阻断Bcl-2激活钙泵的功效可能对治疗坏死以及炎症有益。
Bcl-2是一种凋亡基因。该基因属于线虫ced9基因在哺乳类动物中的同源物，能延长细胞生存，抑制细胞凋亡，但不能促进细胞增殖。（生物谷：Bioon.com）
doi:10.1016/j.cub.2012.05.002
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A Novel Role for Bcl-2 in Regulation of Cellular Calcium Extrusion
Pawel E. Ferdek, Julia V. Gerasimenko, Shuang Peng, Alexei V. Tepikin, Ole H. Petersen, Oleg V. Gerasimenko
The antiapoptotic protein Bcl-2 [1,2] plays important roles in Ca2+ signaling [3] by influencing inositol triphosphate receptors and regulating Ca2+-induced Ca2+ release [4,5,6]. Here we investigated whether Bcl-2 affects Ca2+ extrusion in pancreatic acinar cells. We specifically blocked the Ca2+ pumps in the endoplasmic reticulum and assessed the rate at which the cells reduced an elevated cytosolic Ca2+ concentration after a period of enhanced Ca2+ entry. Because external Ca2+ was removed and endoplasmic reticulum Ca2+ pumps were blocked, Ca2+ extrusion was the only process responsible for recovery. Cells lacking Bcl-2 restored the basal cytosolic Ca2+ level much faster than control cells. The enhanced Ca2+ extrusion in cells from Bcl-2 knockout (Bcl-2 KO) mice was not due to increased Na+/Ca2+ exchange activity, because removal of external Na+ did not influence the Ca2+ extrusion rate. Overexpression of Bcl-2 in the pancreatic acinar cell line AR42J decreased Ca2+ extrusion, whereas silencing Bcl-2 expression (siRNA) had the opposite effect. Loss of Bcl-2, while increasing Ca2+ extrusion, dramatically decreased necrosis and promoted apoptosis induced by oxidative stress, whereas specific inhibition of Ca2+ pumps in the plasma membrane (PMCA) with caloxin 3A1 reduced Ca2+ extrusion and increased necrosis. Bcl-2 regulates PMCA function in pancreatic acinar cells and thereby influences cell fate.
