近日,，研究人員發(fā)現(xiàn)身體如何控制細(xì)胞死亡的一個(gè)新機(jī)制,，這一發(fā)現(xiàn)有利于開(kāi)發(fā)出潛在的新的治療靶標(biāo)。
近來(lái),，加的夫大學(xué)生物科學(xué)學(xué)院的一個(gè)研究小組發(fā)現(xiàn)高酒精攝入可誘發(fā)胰腺炎和胰腺癌的發(fā)生發(fā)展?，F(xiàn)在一項(xiàng)新的發(fā)表在Current Biology雜志上的研究揭示了兩個(gè)眾所周知的分子對(duì)于胰腺炎癥和癌癥的作用機(jī)制。
Cardiff研究團(tuán)隊(duì)探究了蛋白Bcl-2,，Bcl-2已知能夠抑制體內(nèi)所有組織類型的細(xì)胞程序化死亡,。但這項(xiàng)新研究發(fā)現(xiàn)Bcl-2在某些情況下能夠促進(jìn)腫瘤的生長(zhǎng)。
有關(guān)胰腺細(xì)胞的研究表明,，去除Bcl-2能激活細(xì)胞膜上泵出鈣分子的蛋白,。Bcl-2較低水平的話，程序性細(xì)胞死亡的水平增加,。但他們發(fā)現(xiàn),，缺乏Bcl-2能顯著防止另一種更危險(xiǎn)的細(xì)胞死亡形式——壞死。該研究小組發(fā)現(xiàn)Bcl-2增加對(duì)壞死的抑制直接與增加鈣泵的活性有關(guān),。Oleg Gerasimenko博士和Ole Petersen教授率領(lǐng)的團(tuán)隊(duì)認(rèn)為,，阻斷Bcl-2激活鈣泵的功效可能對(duì)治療壞死以及炎癥有益。
Bcl-2是一種凋亡基因,。該基因?qū)儆诰€蟲(chóng)ced9基因在哺乳類動(dòng)物中的同源物,，能延長(zhǎng)細(xì)胞生存，抑制細(xì)胞凋亡,，但不能促進(jìn)細(xì)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.
