Differences between group X and group V secretory phospholipase A 2 in lipolytic modification of lipoproteins

摘要

Secretory phospholipases A 2 (sPLA 2s) are a diverse family of low molecular mass enzymes (13-18 kDa) that hydrolyze the sn-2 fatty acid ester bond of glycerophospholipids to produce free fatty acids and lysophospholipids. We have previously shown that group X sPLA 2 (sPLA 2-X) had a strong hydrolyzing activity toward phosphatidylcholine in low-density lipoprotein (LDL) linked to the formation of lipid droplets in the cytoplasm of macrophages. Here, we show that group V sPLA 2 (sPLA 2-V) can also cause the lipolysis of LDL, but its action differs remarkably from that of sPLA 2-X in several respects. Although sPLA 2-V released almost the same amount of fatty acids from LDL, it released more linoleic acid and less arachidonic acid than sPLA 2-X. In addition, the requirement of Ca 2+ for the lipolysis of LDL was about 10-fold higher for sPLA 2-V than sPLA 2-X. In fact, the release of fatty acids from human serum was hardly detectable upon incubation with sPLA 2-V in the presence of sodium citrate, which contrasted with the potent response to sPLA 2-X. Moreover, sPLA 2-X, but not sPLA 2-V, was found to specifically interact with LDL among the serum proteins, as assessed by gel-filtration chromatography as well as sandwich enzyme-immunosorbent assay using anti-sPLA 2-X and anti-apoB antibodies. Surface plasmon resonance studies have revealed that sPLA2-X can bind to LDL with high-affinity (K d = 3. 1 nM) in the presence of Ca 2+. Selective interaction of sPLA 2-X with LDL might be involved in the efficient hydrolysis of cell surface or intracellular phospholipids during foam cell formation.