Ceramides are generated from sphingomyelin through activation of sphingomyelinases or through the de novo synthesis pathway, which requires coordinate action of serine palmitoyl transferase and ceramide synthase. They have been shown to mediate antiproliferative responses such as apoptosis, growth arrest, differentiation, and senescence. C-16 ceramide is an endogenous ceramide, generated by ceramide synthase 6 (CerS6), that acts a lipid second messenger to regulate apoptosis and stress signaling. Accumulation of C-16 ceramide through PPMP (30 μM) or MAPP (50 μM) treatment or from addition of 100 μM synthetic C-16 ceramide induces apoptosis in neutrophil cultures via caspase-3 activation.
