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.
Department of Biology, University of California, Riverside 92521, USA.
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HW
Huang
E M
EM
Goldberg
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Zidovetzki
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002518:Ceramides / Q000737:chemistry / Q000494:pharmacology*; D004546:Elapid Venoms / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D013329:Structure-Activity Relationship
D002518:Ceramides; D004546:Elapid Venoms; D008051:Lipid Bilayers; D015060:1,2-Dipalmitoylphosphatidylcholine; D010741:Phospholipases A; D054467:Phospholipases A2