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Ceramide is a lipid second messenger that acts on mul-tiple-target enzymes, some of which are involved in other signal-transduction systems. We have previously demon-strated that endogenous ceramide modifies the metabolism of brain ethanolamine plasmalogens. The mechanism involved was studied. On the basis of measurements of breakdown products, specific inhibitor effects, and previ-ous findings, we suggest that a plasmalogen-selective phospholipase A2 is the ceramide target. | Eur. J. Biochem. 270 36-46 2003 FEBS 2003 doi 10.1046 j.1432-1033.2003.03356.x Signaling events mediating activation of brain ethanolamine plasmalogen hydrolysis by ceramide Eduardo Latorre1 M. Pilar Collado1 Inmaculada Fernandez1 M. Dolores Aragones1 and R. Edgardo Catalan2 1 Departamento de Bioquimica y Biologia Molecular I Facultad de Quimicas Universidad Complutense de Madrid Madrid Spain 2Departamento de Biologia Molecular Centro de Biologia Molecular Severo Ochoa Universidad Autonoma de Madrid Madrid Spain Ceramide is a lipid second messenger that acts on multiple-target enzymes some of which are involved in other signal-transduction systems. We have previously demonstrated that endogenous ceramide modifies the metabolism of brain ethanolamine plasmalogens. The mechanism involved was studied. On the basis of measurements of breakdown products specific inhibitor effects and previous findings we suggest that a plasmalogen-selective phospholipase A2 is the ceramide target. Arachidonate-rich pools of the diacylphosphatidylethanolamine subclass were also affected by ceramide but the most affected were plasmalogens. Concomitantly with production of free arachidonate increased 1-O-arachidonoyl ceramide formation was observed. Quinacrine phospholipase A2 inhibitor and 1-O-octadecyl-2-O-methyl-rac-glycerol-3-phosphocholine CoA-independent transacylase inhibitor prevented all of these ceramide-elicited effects. Therefore phospholipase and transacylase activities are tightly coupled. Okadaic acid phosphatase 2A inhibitor and PD 98059 mitogen-activated protein kinase inhibitor modified basal levels of ceramide and sphingomyelinase-induced accumulation of ceramide respectively. Therefore they provided no evidence to determine whether there is a sensitive enzyme downstream of ceramide. The evidence shows that there are serine-dependent and thiol-dependent enzymes downstream of ceramide generation. Furthermore experiments with Ac-DEVD-CMK caspase-3 specific inhibitor have .
