Lin C F, Chen C L, Lin Y S
Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan.
Curr Med Chem. 2006;13(14):1609-16. doi: 10.2174/092986706777441986.
Ceramide, a product of sphingolipid metabolism, is generated in response to various stress stimuli, such as tumor necrosis factor-alpha, CD95/Fas, chemotherapeutic agents, and irradiation. Ceramide may modulate the biochemical and cellular processes that lead to apoptosis. However, the mechanisms by which ceramide regulates apoptotic events are not fully defined. It is believed that the biological effect of ceramide depends on its concentration, the activation or differentiation status of the cell, and the time frame of action. Here, we discuss the metabolism and cell apoptotic signaling of ceramide. The involvement of protein kinases (i.e. PI3K/Akt and GSK-3beta) and protein phosphatases (i.e. PP1 and PP2A), Bcl-2 family proteins, mitochondrial damage, and caspase cascade activation are demonstrated. Further, ceramide and its derivatives have recently been incorporated into strategies for anticancer therapies. An understanding of the apoptotic signaling pathways mediated by ceramide may shed light on its potential for therapeutic intervention.
神经酰胺是鞘脂代谢的产物，在多种应激刺激下产生，如肿瘤坏死因子-α、CD95/Fas、化疗药物和辐射。神经酰胺可能调节导致细胞凋亡的生化和细胞过程。然而，神经酰胺调节凋亡事件的机制尚未完全明确。据信，神经酰胺的生物学效应取决于其浓度、细胞的激活或分化状态以及作用的时间框架。在此，我们讨论神经酰胺的代谢和细胞凋亡信号传导。已证明蛋白激酶（即PI3K/Akt和GSK-3β）和蛋白磷酸酶（即PP1和PP2A）、Bcl-2家族蛋白、线粒体损伤和半胱天冬酶级联激活的参与。此外，神经酰胺及其衍生物最近已被纳入抗癌治疗策略。了解由神经酰胺介导的凋亡信号通路可能有助于揭示其治疗干预的潜力。
