Anjum R, Ali A M, Begum Z, Vanaja J, Khar A
Centre for Cellular and Molecular Biology, Hyderabad, India.
FEBS Lett. 1998 Nov 13;439(1-2):81-4. doi: 10.1016/s0014-5793(98)01343-x.
Ceramide, a product of sphingomyelin metabolism, is a novel lipid second messenger that mediates diverse cellular functions. The present study demonstrates the activation of caspase-3/CPP-32beta, during apoptosis induced by cell permeable exogenous ceramides, in AK-5 tumor, a spontaneously regressing rat histiocytoma. The apoptotic events were suppressed by the caspase-3 specific tetrapeptide inhibitor DEVD-CHO but not by the caspase-1 inhibitor YVAD-CMK. In cells overexpressing Bcl-2, a significant decrease in cell death was observed after exogenous addition of ceramides. Furthermore the processing of caspase-3 to its active form upon apoptotic stimulus, and the subsequent cleavage of the substrate PARP, suggested a central role for caspase-3 in the ceramide mediated apoptosis in AK-5 tumor cells.
神经酰胺是鞘磷脂代谢的产物，是一种介导多种细胞功能的新型脂质第二信使。本研究证明，在可穿透细胞的外源性神经酰胺诱导的细胞凋亡过程中，在AK-5肿瘤（一种自发消退的大鼠组织细胞瘤）中半胱天冬酶-3/CPP-32β被激活。凋亡事件被半胱天冬酶-3特异性四肽抑制剂DEVD-CHO抑制，但未被半胱天冬酶-1抑制剂YVAD-CMK抑制。在过表达Bcl-2的细胞中，外源性添加神经酰胺后观察到细胞死亡显著减少。此外，凋亡刺激后半胱天冬酶-3加工成其活性形式以及随后底物PARP的裂解，表明半胱天冬酶-3在AK-5肿瘤细胞中神经酰胺介导的凋亡中起核心作用。
