Hannun Y A, Obeid L M
Division of Hematology, Duke University Medical Center, Durham, NC.
Trends Biochem Sci. 1995 Feb;20(2):73-7. doi: 10.1016/s0968-0004(00)88961-6.
Recent investigation of the roles of sphingolipids in signal transduction and cell regulation is shedding a new light on the mechanisms of growth suppression and apoptosis. A sphingomyelin cycle has been identified whereby the action of certain extracellular agents (such as tumor necrosis factor alpha) results in activation of a sphingomyelinase, which cleaves membrane sphingomyelin, to generate cellular ceramide. Ceramide, in turn, has emerged as a candidate intracellular mediator for the action of these extracellular agents, and has multiple cellular and biochemical targets. In particular, ceramide is a potent and specific suppressor of cell growth and an inducer of apoptosis. Further studies on this signal transduction pathway should provide new understanding of the physiological functions of ceramide and promise significant insight into a novel biochemical pathway regulating apoptosis.
近期对鞘脂类在信号转导和细胞调节中作用的研究，为生长抑制和细胞凋亡机制带来了新的认识。已确定了一个鞘磷脂循环，某些细胞外因子（如肿瘤坏死因子α）的作用会导致鞘磷脂酶激活，该酶可切割膜鞘磷脂，生成细胞神经酰胺。反过来，神经酰胺已成为这些细胞外因子作用的细胞内介导物候选者，并且有多个细胞和生化靶点。特别是，神经酰胺是细胞生长的有效且特异性抑制剂和细胞凋亡诱导剂。对该信号转导途径的进一步研究应能让我们对神经酰胺的生理功能有新的理解，并有望深入了解调节细胞凋亡的新生化途径。
