Grassmé Heike, Riethmüller Joachim, Gulbins Erich
Institute of Molecular Biology, University of Duisburg-Essen, 45122 Essen, Germany.
Prog Lipid Res. 2007 May-Jul;46(3-4):161-70. doi: 10.1016/j.plipres.2007.03.002. Epub 2007 Mar 31.
Ceramide has been shown to be critically involved in many aspects of cellular responses to receptor-dependent and -independent stimuli. For instance, ceramide was demonstrated to be a central component of the signaling cascades mediating apoptosis after death receptor stimulation, treatment with chemotherapy or exposure to gamma-irradiation or UV-A light. Further studies indicated the importance of ceramide for the infection of mammalian cells with bacterial, viral and parasitic pathogens. Ceramide is released by the activity of acid, neutral or alkaline sphingomyelinases or de novo synthesized. A concept unifying the diverse biological functions of ceramide indicates that ceramide forms distinct membrane domains, named ceramide-enriched membrane domains or platforms. These domains serve the clustering of receptor molecules, the re-organization of signaling proteins, the exclusion of inhibitory signals and, thus, initiate and greatly amplify a primary signal. In addition, ceramide directly interacts with and stimulates intracellular enzymes that may act together with signals initiated in ceramide-enriched membrane domains to transmit signals into a cell.
神经酰胺已被证明在细胞对受体依赖性和非依赖性刺激的多种反应中起着关键作用。例如，神经酰胺被证明是介导死亡受体刺激、化疗、γ射线照射或UV-A光照射后细胞凋亡信号级联反应的核心成分。进一步的研究表明神经酰胺对于细菌、病毒和寄生虫病原体感染哺乳动物细胞具有重要意义。神经酰胺可通过酸性、中性或碱性鞘磷脂酶的活性释放，或通过从头合成产生。一个统一神经酰胺多种生物学功能的概念表明，神经酰胺形成了不同的膜结构域，称为富含神经酰胺的膜结构域或平台。这些结构域有助于受体分子的聚集、信号蛋白的重组、抑制信号的排除，从而启动并极大地放大初级信号。此外，神经酰胺直接与细胞内酶相互作用并刺激这些酶，这些酶可能与在富含神经酰胺的膜结构域中启动的信号共同作用，将信号传递到细胞内。
