Ceramides and

The major glycohpids found in animal tissues are glycosphingohpids. They contain ceramide and one or more sugars. Galactosylceramide is a major glyco-... 

Buccliero, R. and Futerman, H. The roles of ceramide and complex sphingolipids in neuronal cell function. Pharm. Res. 47 409-419, 2003. 

Once apoptosis is triggered, a stereotyped sequence of premitochondrial events occurs that executes the cell death process. In many cases proteins and/or lipid mediators that induce changes in mitochondrial membrane permeability and calcium regulation are produced or activated. For example, the pro-apoptotic Bcl-2 family members Bax, Bad and Bid may associate with the mitochondrial membrane and modify its permeability. Membrane-derived lipid mediators such as ceramide and 4-hydroxynonenal can also induce mitochondrial membrane alterations that are critical for the execution of apoptosis. 

Cutler, R. G., Kelly, J., Storie, K. et al. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer s disease. Proc. Natl Acad. Sci. U.S.A. 101 2070-2075,2004. 

Figure 12.12 Sphingomyelins. Sphingomyelins are esters of a ceramide and phospho-ryl choline. However, similar compounds are ceramide-1-phosphoryl ethanolamines and phosphono forms of sphingolipids. Ceramides W-acyl-sphingosines) are amides of a long chain di- or trihydroxy base containing 12 to 22 carbon atoms, of which sphingosine (4-sphingenine) is the commonest, and a long chain fatty acid whose acyl chain is shown by R1. This may contain up to 26 carbon atoms.

Figure 1. Scheme of sphingolipid metabolism and the central role of ceramide and ceramidases. 

Kroesen, B., Pettus, B., Luberto, C., Busman, M., Sietsma, H., De Leij, L., and Hannun, Y.A., 2001, Induction of apoptosis through B-ceU receptor crosslinking occurs via de novo generated C16 ceramide and involves mitochondria. J. Biol. Chem. pubhshed January 17, 2001 as 10.1074/jbc.M009517200. 

Muller, G., Ayoub, M., Storz, P., Rennecke, J., Fabbro, D., Pfizenmaier, K., 1995, PKC zeta is a molecular switch in signal transduction of TNF-alpha, bifunctionally regulated by ceramide and arachidonic acid. EMBOJ. 14 1961-1969. 

Welsh, N., 1996, Interleukin-l-induced ceramide and diacylglycerol generation may lead to activation of the c-Jun NH2-terminal kinase and the transcription factor ATF2 in the insulin-producing cell fine RINm5F. J. Biol. Chem. 271 8307-8312. 

Cross-talk between ceramide and phospholipid biosynthesis... 

Figure 2. Effect of Ca-ceramide on phosphatidylcholine and phosphatidylethanolamine synthesis in rat-2 fibroblasts. Cells were treated for 2 h in the absence (open bars) or presence (hatched bars) of 25pM C6-ceramide and the following parameters were determined i) the incorporation of [ H]choline and [ H]ethanolamine into phosphatidylcholine (PC) and phosphatidylethanolamine (PE), respectively (panel A) and in CDP-choline and CDP-ethanolamine, respectively (panel B) and ii) the in vitro activity of choline- and ethanolaminephosphotransferase (CPT and EPT) (panel C).

SMase activity (Mansat et al 1997) and downstream (by blocking the apoptotic effect of ceramide). However, the cross-talk between ceramides and DAG opens new intriguing avenues of research and may lead to better pharmacological maiupulation of key steps in the apoptosis/survival signaling cascade resulting in an increased chemosensitivity of neoplastic cells. 

Allan, D., 2000, Lipid metabolic changes caused by short-chain ceramides and the connection with apoptosis. Biochem. J. 345 603-610... 

Yen, C.L., Mar, M.H., and Zeisel, S.H., 1999, Chohne dehdency-induced apoptosis in PC12 ceUs is associated with diminished membrane phosphatidylcholine and sphingomyelin, accumulation of ceramide and diacylglycetol, and achvation of a caspase. FASEB. J. 13 135-142... 

A variety of studies demonstrate a central role for ASM and ceramide in several forms of apoptosis. Ceramide seems to regulate the activity of certain proteins and, thus, may function, in some circumstances, as a second messenger. In addition, the concept of raft modification hy ceramide provides a comprehensive model for cellular effects of ceramide, and perhaps a biophysical explanation for the diverse functions of this lipid. 

Luberto, C., and Hannun, Y. A., 1998, Sphingomyelin synthase, a potential regulator of intracellular levels of ceramide and diacylglycerol during SV40 transformation. Does sphingomyelin synthase account for the putative phosphatidylcholine-specific phospholipaseC /. Biol. Chem. 273 14550-14559. 

Yu, Z. P., Nikolova-KarakasMan, M., Zhou, D., Cheng, G., Schuchman, E. H., and Mattson, M. p., 2000, Pivotal rale for acidic sphingomyehnase in cerebral ischemia-induced ceramide and cytokine production, and neuronal apoptosis. J Mol Neuroscience 15 85-97. 

Kolesnick R, Hannun YA (1999) Ceramide and apoptosis. Trends Biochem Sci 282 224-225... 

Haimovitz-Friedman A, Kan CC, Ehleiter D, et al. Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J Exp Med 1994 180 525-535. 

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