Schenck Marcus, Carpinteiro Alexander, Grassmé Heike, Lang Florian, Gulbins Erich
Institute of Molecular Biology, University of Duisburg-Essen, Hufelandstrasse 55, D45122 Essen, Germany.
Arch Biochem Biophys. 2007 Jun 15;462(2):171-5. doi: 10.1016/j.abb.2007.03.031. Epub 2007 Apr 11.
Ceramide generated in the cell membrane has been shown to be central for the induction of apoptosis by death receptors and many stress stimuli such as gamma-irradiation, UV-light or infection with pathogens. Ceramide reorganizes cell membranes and forms large ceramide-enriched membrane domains that serve the spatial and temporal organization of the cellular signalosome upon activation. Thus, ceramide-enriched membrane domains mediate clustering of CD95 and DR5 to facilitate apoptosis, and they are also critically involved in apoptosis after irradiation, UV-light and infection with Pseudomonas aeruginosa. Since ceramide-enriched membrane domains amplify signals, their function is not restricted to the induction of apoptosis and it was shown that ceramide-enriched membrane domains are also involved in internalization of pathogens and the control of cytokine release from infected epithelial cells. Recent studies support the notion that changes of the ceramide metabolism are also critically involved in human diseases, for instance neurological disorders, cancer, infectious diseases and Wilson's disease.
细胞膜中生成的神经酰胺已被证明是死亡受体诱导细胞凋亡以及许多应激刺激（如γ射线照射、紫外线照射或病原体感染）诱导细胞凋亡的核心因素。神经酰胺会重组细胞膜并形成富含神经酰胺的大膜结构域，这些结构域在激活时为细胞信号体提供空间和时间上的组织。因此，富含神经酰胺的膜结构域介导CD95和DR5的聚集以促进细胞凋亡，并且它们在辐射、紫外线照射以及铜绿假单胞菌感染后的细胞凋亡中也起着关键作用。由于富含神经酰胺的膜结构域会放大信号，其功能并不局限于诱导细胞凋亡，并且已表明富含神经酰胺的膜结构域还参与病原体的内化以及受感染上皮细胞中细胞因子释放的控制。最近的研究支持这样一种观点，即神经酰胺代谢的变化在人类疾病（如神经疾病、癌症、传染病和威尔逊氏病）中也起着关键作用。
