Bimodal regulatory effect of melittin and phospholipase A2-activating protein on human type II secretory phospholipase A2.
Melittin and phospholipase A2-activating protein (PLAP) are known as efficient activators of secretory phospholipase A2(sPLA2) types I, II, and III when phospholipid liposomes are used as substrate. The present study demonstrates that both peptides can either inhibit or activate sPLA2 depending on the peptide/phospholipid ratio when erythrocyte membranes serve as a biologically relevant substrate. Low concentrations of melittin and PLAP were observed to inhibit sPLA2-triggered release of fatty acids from erythrocyte membranes. The inhibition was reversed at melittin concentrations above 1 microM. PLAP-induced inhibition of sPLA2 persisted steadily throughout the used concentration range (0-150 nM). The two peptides induced a dose-dependent activation of sPLA2 at low concentrations, followed by inhibition when model membranes were used as substrate. This opposite modulatory effect on biological membranes and model membranes is discussed with respect to different mechanisms the interaction of the regulatory peptides with the enzyme molecules and the substrate vesicles.
D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology; D005227:Fatty Acids / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D054501:Group II Phospholipases A2; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008555:Melitten / Q000096:biosynthesis / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D010741:Phospholipases A / Q000096:biosynthesis* / Q000378:metabolism; D054467:Phospholipases A2; D011506:Proteins / Q000378:metabolism*; D013696:Temperature; D013997:Time Factors
D005227:Fatty Acids; D008081:Liposomes; D010455:Peptides; D011506:Proteins; C055324:phospholipase A2-activating protein; D008555:Melitten; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2