Liu G, Kleine L, Hébert R L
Department of Cellular and Molecular Medicine, University of Ottawa, Ontario, Canada.
Crit Rev Clin Lab Sci. 1999 Dec;36(6):511-73. doi: 10.1080/10408369991239240.
Recently, the sphingolipid metabolites ceramide, sphingosine, ceramide 1-P, and sphingosine 1-P have been implicated as second messengers involved in many different cellular functions. Publications on this topic are appearing at a rapidly increasing rate and new developments in this field are also appearing rapidly. It is thus important to summarize the results obtained from many different laboratories and from different fields of research to obtain a clearer picture of the importance of sphingolipid metabolites. This article reviews the studies from the last few years and includes the effects of a variety of extracellular agents on sphingolipid signal transduction pathways in different tissues and cells and on the mechanisms of regulation. Sphingomyelin exists in a number of functionally distinct pools and is composed of distinct molecular species. Sphingomyelin metabolites may be formed by many different pathways. For example, the generation of ceramide from sphingomyelin can be catalyzed by at least five different sphingomyelinases. A large variety of stimuli can induce the generation of ceramide, leading to activation or inhibition of various cellular events such as proliferation, differentiation, apoptosis, and inflammation. The effect of ceramide on these physiological processes is due to its many different downstream targets. It can activate ceramide-activated protein kinases and ceramide-activated protein phosphatases. It also activates or inhibits PKCs, PLD, PLA2, PC-PLC, nitric oxide synthase, and the ERK and SAPK/JNK signaling cascades. Ceramide activates or inhibits transcription factors, modulates calcium homeostasis and interacts with the retinoblastoma protein to regulate cell cycle progression. Most of the work in this field has involved the study of ceramide effects, but the roles of the other three sphingomyelin metabolites is now attracting much attention. The complex interactions between signaling components and ceramide and the controls regulating these interactions are now being identified and are presented in this review.
最近，鞘脂代谢产物神经酰胺、鞘氨醇、神经酰胺-1-磷酸和鞘氨醇-1-磷酸被认为是参与多种不同细胞功能的第二信使。关于这一主题的出版物数量正在迅速增加，该领域的新进展也层出不穷。因此，总结来自许多不同实验室和不同研究领域的结果，以更清楚地了解鞘脂代谢产物的重要性非常重要。本文回顾了过去几年的研究，包括多种细胞外因子对不同组织和细胞中鞘脂信号转导途径的影响以及调节机制。鞘磷脂存在于许多功能不同的池中，由不同的分子种类组成。鞘磷脂代谢产物可能通过许多不同的途径形成。例如，鞘磷脂生成神经酰胺可由至少五种不同的鞘磷脂酶催化。多种刺激可诱导神经酰胺的生成，导致各种细胞事件如增殖、分化、凋亡和炎症的激活或抑制。神经酰胺对这些生理过程的影响归因于其许多不同的下游靶点。它可激活神经酰胺激活的蛋白激酶和神经酰胺激活的蛋白磷酸酶。它还可激活或抑制蛋白激酶C、磷脂酶D、磷脂酶A2、磷脂酰胆碱-磷脂酶C、一氧化氮合酶以及细胞外信号调节激酶和应激激活蛋白激酶/应激活化蛋白激酶信号级联反应。神经酰胺激活或抑制转录因子，调节钙稳态，并与视网膜母细胞瘤蛋白相互作用以调节细胞周期进程。该领域的大多数工作都涉及对神经酰胺作用的研究，但其他三种鞘磷脂代谢产物的作用现在也备受关注。信号成分与神经酰胺之间的复杂相互作用以及调节这些相互作用的控制机制目前正在被确定，并在本综述中呈现。
