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lüll Ceramide signaling in apoptosis Haimovitz-Friedman A; Kolesnick RN; Fuks ZBr Med Bull 1997[]; 53 (3): 539-53The sphingomyelin pathway is a ubiquitous, evolutionarily conserved signaling system initiated by hydrolysis of the plasma membrane phospholipid sphingomyelin to generate ceramide. Ceramide acts as a second messenger in activating the apoptotic cascade. Diverse cytokine receptors and environmental stresses utilize ceramide to signal apoptosis. In several cell systems ceramide links to the stress-activated protein kinase (SAPK)/c-jun kinase (JNK) cascade to signal apoptosis. The engagement of the sphingomyelin pathway in signaling apoptosis is tightly regulated by anti-apoptotic control mechanisms, and the balance between pro- and anti-apoptotic systems determines the magnitude of the apoptotic response in vitro and in vivo. This review describes the known elements and molecular ordering of ceramide-mediated apoptosis and the anti-apoptotic mechanisms that regulate its expression. Understanding of pro- and anti-apoptotic signaling involved in ceramide-mediated apoptosis and the modes of their co-ordinated function may yield opportunities for pharmacological interventions with potential for clinical applications.|*Caspases[MESH]|Apoptosis/*physiology[MESH]|Caenorhabditis elegans Proteins[MESH]|Caspase 1[MESH]|Ceramides/*physiology[MESH]|Cysteine Endopeptidases/physiology[MESH]|Fibroblast Growth Factor 2/physiology[MESH]|Humans[MESH]|Signal Transduction/*physiology[MESH]|Sphingomyelins/physiology[MESH] |