Differences between group X and group V secretory phospholipase A2 in lipolytic modification of lipoproteins

Abstract

Secretory phospholipases A 2 (sPLA 2 s) 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 sPLA 2 -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.

The dual role of group V secretory phospholipase A2 in pancreatic β-cells

“…Thus, compartmentalization of GX sPLA 2 activity may be dictated by the subcellular location of the activating convertase. It is also important to note that local Ca 2+ concentrations may influence the relative hydrolytic activity of the two enzymes, since in vitro studies indicate the requirement for Ca 2+ is 10-fold higher for GV sPLA 2 compared to GX sPLA 2 [46]. Clearly, additional studies are required to determine whether spatial segregation of the catalytic activities of Group V and Group X sPLA 2 is responsible for the observed functional differences of these two enzymes in β-cells.…”