Partial coverage of phospholipid model membranes with annexin V may completely inhibit their degradation by phospholipase A2.
Phospholipase A2 (PLA2)-mediated hydrolysis of membrane phospholipids was measured by ellipsometry, and the inhibition of this process by annexin V was studied. Planar membranes, consisting of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine (PC/PE/PS; 54:33:13, on molar basis), were degraded by pancreatic PLA2, and the rate of hydrolysis was limited to about 0.7%/min. The influence of graded coverage of the membrane with annexin V was studied. The degree of PLA2 inhibition was nonlinearly related to the amount of membrane-bound annexin V, and binding of only 12% and 54% of full membrane coverage resulted in, respectively, 50% and 93% inhibition. These findings indicate that the inhibition of PLA2-mediated hydrolysis by annexin V cannot be simply explained by shielding of phospholipid substrates from the enzyme. Moreover, the present results leave room for a role of endogenous annexin V in regulating phospholipid turnover in the plasma membrane of parenchymal cells such as cardiomyocytes.
Speijer
H
H
Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands.
Jans
S W
SW
Reutelingsperger
C P
CP
Hack
C E
CE
van der Vusse
G J
GJ
Hermens
W T
WT
D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology*; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D010179:Pancreas / Q000201:enzymology; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D013499:Surface Properties; D013552:Swine
D017304:Annexin A5; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; C042511:1,2-dioleoylphosphatidylserine; C020888:1,2-dielaidoylphosphatidylethanolamine; D010741:Phospholipases A; D054467:Phospholipases A2; C017251:1,2-oleoylphosphatidylcholine