Cell Biology International (2003) 27, 871877 (Printed in Great Britain)
Bimodal regulatory effect of melittin and phospholipase A2-activating protein on human type II secretory phospholipase A2
K Koumanova*, A Momchilovaa and C Wolfb
aInstitute of Biophysics, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
bService de Biochimie, URA CNRS 1283, Faculté de Médecine Saint-Antoine, 75012 Paris, France
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 sPLA2depending 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 μM. PLAP-induced inhibition of sPLA2persisted steadily throughout the used concentration range (0–150 nM). The two peptides induced a dose-dependent activation of sPLA2at 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.
Key words: Melittin, Phospholipase A2-activating protein (PLAP), Secretory phospholipase A2.
Received 3 April 2003/20 May 2003; accepted 14 July 2003