LDL-associated phospholipase a does not protect LDL against lipid peroxidation in vitro

Edit Schnitzer, Ilya Pinchuk, Menachem Fainaru, Dov Lichtenberg, Saul Yedgar

Research output: Contribution to journalArticlepeer-review

Abstract

The irreversible proteinase inhibitor Pefabloc (4-[2-aminoethyl] benzenesulfonyl fluoride) inactivates LDL-catalyzed hydrolysis of the short- chain fluorescent phospholipid C6-NBD-PC (1-acyl-2-(N-4-nitrobenzo-2-oxa- 1,3-diazole)-aminocaproyl phosphatidylcholine). The dose-dependence of this inactivation is similar to that obtained previously for the inhibitory effect of Pefabloc on the hydrolysis of platelet activating factor (PAF) by the LDL- associated PAF acetylhydrolase (PAF-AH), in agreement with the notion that the hydrolysis of C6-NBD-PC and PAF is catalyzed by the same enzyme (LDL- associated phospholipase A; LDL-PLA). This conclusion is also supported by the finding that hydrolysis of C6-NBD-PC by LDL becomes inactivated by LDL oxidation only at late stages of the oxidation, similar to the effect of oxidation on the hydrolysis of PAF by the LDL-associated PAF-AH. Under conditions of complete inactivation of this enzyme towards C6-NBD-PC, the kinetics of lipid peroxidation, induced either by copper ions or by the free radical generator AAPH at varying doses of the prooxidant, was similar to that observed when the PLA was active (i.e., in the absence of Pefabloc). Hence, LDL-associated PLA (PAF-AH) does not protect LDL lipids from peroxidation. Similar results were obtained with fractionated LDL in albumin- containing buffer and for non-fractionated serum, in which copper-induced peroxidation was also not influenced by inactivation of the enzyme responsible for hydrolysis of C6-NBD-PC. Phospholipolysis of short chain phospholipids by LDL-PLA may still play a protective role against the toxic effects of oxidized phospholipids by reducing their internalization into cells (Schmitt et al. 1995).

Original languageEnglish
Pages (from-to)1294-1303
Number of pages10
JournalFree Radical Biology and Medicine
Volume24
Issue number7-8
DOIs
StatePublished - May 1998

Keywords

  • 1-Acyl-2-(N-4-nitrobenzo-2-oxa-1,3- diazole)-aminocaproyl phosphatidylcholine (CNBD-PC)
  • Free radical
  • LDL- associated phospholipase A (LDL-PLA or LDL-PLA) Platelet activating factor (PAF)
  • Lipid peroxidation
  • Low density lipoproteins (LDL)
  • PAF acetylhydrolase (PAF-AH)
  • Pefabloc (4-[2- aminoethyl]benzenesulfonyl fluoride)

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