溶酶体蛋白酶cathepsin B参与介导前列腺癌PC-3细胞凋亡  

Apoptosis of Human Prostate Cancer PC-3 Cells is Mediated by Lysosomal Cathepsin B

作　　者：纪汪溟[1] 刘建平[1] 

机构地区：[1]复旦大学生命科学学院遗传工程国家重点实验室,上海200433

出　　处：《复旦学报（自然科学版）》2012年第3期269-275,共7页Journal of Fudan University：Natural Science

基　　金：国家自然科学基金资助项目(30771051)

摘　　要：细胞凋亡是多细胞生物清除多余、损伤或有潜在危险细胞的一种主要生理机制.蛋白水解酶是细胞凋亡研究的重要对象,其中大部分工作都集中在探索caspases的功能和调控上.近年来,越来越多的证据显示一些非caspases蛋白酶如位于溶酶体中的cathepsins特别是cathepsin B(CTSB)参与细胞凋亡过程.溶酶体cathepsins既可以与caspases协同作用,也可以不依赖于caspases独立执行凋亡功能.选取人前列腺癌PC-3细胞株作为研究对象,通过检测PC-3细胞对TNFα、D-sphingosine两种凋亡诱导剂和caspases、cathepsins抑制剂的应答反应,以及细胞凋亡过程中溶酶体、线粒体的结构变化,证实了D-sphingosine引起PC-3细胞死亡的效应主要通过释放溶酶体中蛋白酶CTSB实现,CTSB和caspases均参与介导TNFα诱导的PC-3细胞凋亡过程,并且很可能在不同的凋亡信号通路中发挥作用.Apoptosis is the major mechanism by which multicellular organisms clear superfluous, infected, damaged or potentially dangerous cells. The roles of proteolytic enzymes in the regulation of apoptosis were major research topics. Most of the studies were focused on the role and regulation of caspases, which may be indispensable for the typical apoptotic pathway. In recent years, there has been a growing body of evidence to suggest that, in addition to caspases, other proteases, such as cathepsins, may also be involved in apoptosis. Lysosomal cathepsins, in particular cathespin B（CTSB）, have been reported to activate caspase-dependent and- independent pathways of cell death. The purpose of this study was to investigate the mechanism of apoptosis in human prostate cancer PC-3 cells. It was showed that both eathepsin B and easpases participated in TNFa-indueed apoptosis in PC-3 cells. Cell death induced by TNFa was suppressed by the pretreatment with inhibitors of mituchondria permeability transition and lysosomal cathepsins. Copreincubation with cathepsin B specific inhibitor CA074Me and pan caspases inhibitor z- VAD-fmk prevented PC-3 cell apoptosis more efficiently than CA074Me or z-VAD-fmk did separately. In addition, inhibition of cathepsin B activity profoundly protected PC-3 cells against D-sphingosine-induced death. These results demonstrate that TNFα-induced apoptosis in PC-3 cells is both cathepsin B-and caspases-dependent, and cathepsin B plays a key role in PC-3 cell death induced by D-sphingosine.

关 键 词：细胞凋亡 PC-3细胞 CASPASES CATHEPSIN B TNFα D-sphingosine 

分 类 号：Q279[生物学—细胞生物学]