MEMBRANE LEAKAGE INDUCED BY SYNERGETIC ACTION OF LYS-49 AND ASP-49 AGKISTRODON PISCIVORUS PISCIVORUS PHOSPHOLIPASES A(2) - IMPLICATIONS IN THEIR PHARMACOLOGICAL ACTIVITIES
Z. Shen et Wh. Cho, MEMBRANE LEAKAGE INDUCED BY SYNERGETIC ACTION OF LYS-49 AND ASP-49 AGKISTRODON PISCIVORUS PISCIVORUS PHOSPHOLIPASES A(2) - IMPLICATIONS IN THEIR PHARMACOLOGICAL ACTIVITIES, International journal of biochemistry & cell biology, 27(10), 1995, pp. 1009-1013
To understand the mechanism by which Lys-49 phospholipase A(2) from th
e venom of Agkistrodon piscivorus piscivorus exerts its myotoxic activ
ities, we studied the interactions of this non-catalytic phospholipase
A(2) with various phospholipid monolayers and liposomes, We measured
the interactions of A. p. piscivorus Lys-49 phospholipase A(2) with ph
ospholipid monolayers in terms of the change in surface pressure of mo
nolayer and with liposomes in terms of the leakage of 6-carboxyfluores
cein trapped in liposomes, A. p. piscivorus Lys-49 phospholipase A(2)
showed the ability to rapidly acid extensively induce the leakage of 6
-carboxyfluorescein from anionic liposomes. The extent of leakage was
sensitive to the ionic strength of medium and the surface charge densi
ty of liposomes, indicating the electrostatic nature of the interactio
ns, Also, this protein was able to penetrate into anionic phospholipid
monolayers with surface pressure of up to 38 dyn/cm, indicating the i
nvolvement of hydrophobic interactions in its binding to anionic lipos
omes. Another phospholipase A(2) from the same venom, Asp-49 phospholi
pase A(2), was shown to assist the lytic activity of Lys-49 phospholip
ase A(2) toward neutral liposomes by hydrolytically generating anionic
patches of reaction products on the liposome surface, These results i
ndicate that Lys-49 phospholipase A(2) binds to and disrupts anionic m
embranes via both electrostatic and hydrophobic interactions and that
two phospholipases A(2) from the same venom work synergetically to enh
ance their pharmacological activities.