[The effect of LDL on the activity of proinflammatory secretory phospholipase A2 (IIA) depends on the degree of their oxidation].
Phospholipase A2 group IIA which is secreted in inflammation [secPLA2(IIA)] does not always exhibit catalytic activity, although being present in patients' serum. The mechanisms regulating the enzyme activity in peripheral blood have not been studied in sufficient detail. In this study we examined the effects of native and oxidized LDL with varied degree of oxidation on secPLA2(IIA) from human heart myxoma. The degree of LDL oxidation was evaluated from the amount of conjugated dienes and lysophosphatidylcholine. Liposomes containing radio-labelled phosphatidylcholine were used as a substrate in the secPLA2(IIA) activity assay. Native LDL isolated from serum of healthy subjects inhibited secPLA2(IIA) in a dose-dependent manner. Minimally and moderately oxidized LDL in which < 40 % phosphatidylcholine was hydrolysed to lysophosphatidylcholine activated secPL2(IIA). Strongly oxidized LDL in which > 40 % phosphatidylcholine was hydrolysed to lysophosphatidylcholine inhibited the enzyme. Thus, our findings indicate that the characteristics of circulating lipoproteins are changed by their oxidation. Minimal and moderate oxidation of LDL results in activation of secPLA2(IIA), while strong oxidation causes inhibition of the enzyme. Since inflammation leads to an increase in secPLA2(IIA) secretion and LDL oxidation, the results obtained can be used for the diagnostics of inflammatory processes and provide more insight into molecular mechanisms underlying the development of atherosclerosis.
Korotaeva
A A
AA
Samoĭlova
E V
EV
Pirkova
A A
AA
Prokazova
N V
NV
D002250:Carbon Radioisotopes; D002384:Catalysis; D004305:Dose-Response Relationship, Drug; D054501:Group II Phospholipases A2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006338:Heart Neoplasms / Q000201:enzymology; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D008081:Liposomes; D009232:Myxoma / Q000201:enzymology; D010084:Oxidation-Reduction
D002250:Carbon Radioisotopes; D008077:Lipoproteins, LDL; D008081:Liposomes; C099252:oxidized low density lipoprotein; D054501:Group II Phospholipases A2