Sphingomyelinase

Massing U, Eibl H (1994) Substrates for phospholipase C and sphingomyelinase from Bacillus cereus. In Woolley P, Petersen SB (eds) Lipases. Their structure, biochemistry and application. Cambridge University Press, Cambridge, p 225... 

Auge, N., Nikolova-Karakashian, M., Carpentier, S., Parthasarathy, S., Negre-Salvayre, A., Salvayre, R., Merrill, A.H. Jr, Levade, T, 1999, Role of sphingosine 1-phosphate in the mitogenesis induced by oxidized LDL in smooth muscle cells via activation of sphingomyelinase, ceramidase, and sphingosine kinase, J. Biol. Chem. 274 21533-21538. 

It is important to note that these reverse activities of CDases are distinct from the major CoA-dependent ceramide synthase activity that is present in the ER and is thought to be responsible for de novo synthesis of Cer. Further, this reverse activity of CDases, may emerge as a new pathway of Cer formation, different from the known de novo or sphingomyelinases pathways. 

Similar observahons on the role of CDases were also obtained in rat renal mesangial cells shmulated with TNFa or nihic oxide donors. Both of these agonists were shown to stimulate sphingomyelinases, but only nitric oxide donors inhibited CDases and resulted in an increase in Cer levels and DNA fragmentahon (Huwiler et al., 1999). 

In another line of inveshgation, Auge et al. (1999) showed that heatment of vascular smooth muscle cells with oxidized LDL shmulated sphingomyelinases, CDases, and sphingosine kinase achvihes, leading to the production of SIP which as these authors suggested, promotes the proliferation of these cells. 

Coroneos, E., Martinez, M., McKenna, S. and Kester, M., 1995, Differential regulation of sphingomyelinase and ceramidase activities by growth factors and cytokines. Implications for cellular proliferation and differentiation./.B/oZ.Clrem. 270 23305-23309. 

Figure 1. Pathways for the synthesis of phosphatidylcholine, phosphatidylethanolamine and sphingomyelin. Abbreviations CK, choline kinase CPT, cholinephosphotransferase CT, CTP phosphooholine cytidylyltransferase DAG, diacylglycerol PC, phosphatidylcholine PE, phosphatidylethanolamine PEMT, phosphatidylethanolamine-N-methyltransferase SM, sphingomyelin SMase, sphingomyelinase SMsyn, sphingomyelin synthase.

Figure 4. Cartoon showing the role of the diacylglycerol to ceramide ratio in determining the fate of cells. Abbreviations CER, ceramide DAG, diacylglycerol PLC, phospholipase C PLD, phospholipase D SMase, sphingomyelinase.

Acid Sphingomyelinase-derived Ceramide Signaling in Apoptosis... 

Figure I. Displayed are the structures of sphingomyelin and ceramide. Sphingomyelinases function as phospholipases C to hydrolyze sphingomyelin.

Cellular ceramide is generated either by hydrolysis of sphingomyelin or by de novo synthesis. Sphingomyelin hydrolysis is catalyzed by at least three different sphingomyelinases that are discriminated by their optimal pH acid, neutral, and alkaline sphingomyelinases. In the present manuscript we will focus on acid sphingomyelinase (ASM)-released ceramide. 

Brenner, B., Ferlinz, K., Grassme, H., WeUer, M., Koppenhoefer, U., Dichgans, J., Sandhoff, K. Lang, F. and Gulbins, E., 1998, Fas/CD95/Apo-l activates the acidic sphingomyelinase via caspases. Cell Death Dijfer. 5 29-37... 

Chatterjee, M. and Wu, S., 2001, Involvement of Fas receptor and not tumor necrosis factor-alpha receptor in ultraviolet-induced activation of acid sphingomyelinase. Mol. Carcinog. 30 47-55. 

Holopainen, J.M., Subramanian, M. and Kinnunen, P.K., 1998, Sphingomyelinase induces Upid microdomain formation in a fluid phosphatidychohne/sphingomyelin membrane. Biochemistry 37 17562-17570... 

Huang, C., Wy, M., Ding, M., Bowden, G.T. and Dong, Z., 1997, Direct evidence for an important role of sphingomyelinase in ultraviolet-induced ctivation of c-Jun N-terminal kinase. J. Biol. Chem. 272 21153-21151... 

Kirschnek, S., Paris, R, WeUer, M., Grassme, H., Rerhnz, K., Riehle, A., Fuks, Z., Kolesnick, R. and Gulbins, E., 2000, CD95-mediated apoptosis in vivo involves acid sphingomyelinase. J. Biol. Chem. 275 27316-27323... 

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