Radin N S
Mental Health Research Institute, University of Michigan, Ann Arbor, MI, USA.
Eur J Biochem. 2001 Jan;268(2):193-204. doi: 10.1046/j.1432-1033.2001.01845.x.
Many papers have shown that sphingolipids control the balance in cells between growth and proliferation, and cell death by apoptosis. Sphingosine-1-phosphate (Sph1P) and glucosylceramide (GlcCer) induce proliferation processes, and ceramide (Cer), a metabolic intermediate between the two, induces apoptosis. In cancers, the balance seems to have come undone and it should be possible to kill the cells by enhancing the processes that lead to ceramide accumulation. The two control systems are intertwined, modulated by a variety of agents affecting the activities of the enzymes in Cer-GlcCer-Sph1P interdependence. It is proposed that successful cancer chemotherapy requires the use of many agents to elevate ceramide levels adequately. This review updates current knowledge of sphingolipid metabolism and some of the evidence showing that ceramide plays a causal role in apoptosis induction, as well as a chemotherapeutic agent.
许多论文表明，鞘脂可控制细胞生长与增殖以及细胞凋亡导致的细胞死亡之间的平衡。1-磷酸鞘氨醇（Sph1P）和葡萄糖神经酰胺（GlcCer）诱导增殖过程，而二者之间的代谢中间体神经酰胺（Cer）则诱导细胞凋亡。在癌症中，这种平衡似乎已被打破，通过增强导致神经酰胺积累的过程来杀死细胞应该是可行的。这两个控制系统相互交织，受到多种影响Cer-GlcCer-Sph1P相互依存关系中酶活性的因子的调节。有人提出，成功的癌症化疗需要使用多种药物来充分提高神经酰胺水平。本综述更新了鞘脂代谢的现有知识，以及一些表明神经酰胺在诱导细胞凋亡中起因果作用以及作为化疗药物的证据。
