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

Cell Mol Biol Lett. 2012 Sep;17(3):459-78. doi: 10.2478/s11658-012-0019-2. Epub 2012 Jun 13.

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 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.

MeSH terms

  • Arachidonic Acid* / chemistry
  • Arachidonic Acid* / metabolism
  • Calcium / chemistry
  • Citrates / chemistry
  • Group V Phospholipases A2 / chemistry
  • Group V Phospholipases A2 / metabolism*
  • Group X Phospholipases A2 / chemistry
  • Group X Phospholipases A2 / metabolism*
  • Humans
  • Hydrolysis
  • Linoleic Acid* / chemistry
  • Linoleic Acid* / metabolism
  • Lipolysis
  • Lipoproteins
  • Lipoproteins, HDL* / chemistry
  • Lipoproteins, HDL* / metabolism
  • Lipoproteins, LDL* / chemistry
  • Lipoproteins, LDL* / metabolism
  • Phospholipids / chemistry
  • Phospholipids / metabolism
  • Protein Binding
  • Serum / chemistry
  • Serum / metabolism
  • Sodium Citrate
  • Surface Plasmon Resonance

Substances

  • Citrates
  • Lipoproteins
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Phospholipids
  • Sodium Citrate
  • Arachidonic Acid
  • Linoleic Acid
  • Group V Phospholipases A2
  • Group X Phospholipases A2
  • Calcium