Ceramides perturb the structure of phosphatidylcholine bilayers and modulate the activity of phospholipase A2.

The effects of a series of ceramide analogs with acyl chain lengths of 2, 6, 8 and 16 on the structure of diapalmitoylphosphatidylcholine (DPPC) bilayers and cobra venom phospholipase A2 (PL-A2) activity were studied using 2H-NMR and specific enzymatic assays. C2-ceramide did not induce a significant effect on the structure of DPPC bilayers and did not alter PL-A2 activity. C6- and C8-ceramides increased the ordering of the DPPC acyl chains, correlating with the inhibition of PL-A2 activity which was probably due to the increased lateral surface pressure. The long-chain C16-ceramide induced lateral phase separation of the bilayers into gel and liquid crystalline domains and activated PL-A2, as does natural ceramide (Huang et al. 1996). Taken together, the results strongly suggest a correlation between membrane defects induced by ceramide analogs and their effects on phospholipase A2 activity. Furthermore, the effects of short-chain ceramides on PL-A2 are different from those of natural ceramide, indicating that the cell-permeable short-chain ceramide analogs, widely used to study the shpingomyelin-dependent cellular signal transduction pathway, may not completely mimic the natural product.