Oxidized phosphatidylcholine stimulates activity of secretory phospholipase A2 group IIA and abolishes sphingomyelin-induced inhibition of the enzyme.
We have shown recently that oxidized but not native lipoproteins stimulate the activity of secretory phospholipase A2 group IIA (sPLA(2)(IIA)). Since oxidized lipoproteins potentially contain considerable amounts of oxidized phosphatidylcholine, we examined the effect of oxidized palmitoyl arachidonyl phosphatidylcholine (oxPC) and the competitive effects of oxPC and sphingomyelin (SM) on sPLA(2)(IIA) activity. OxPC either added to the assay medium as separated liposomes or incorporated in varied amounts into LDL progressively enhanced the activity of purified human sPLA(2)(IIA) and abolished the inhibitory effect of LDL-incorporated SM on the enzyme activity. OxPC completely abolished the inhibitory effect of SM at the oxPC/SM concentration ratio 1/2. On the other hand, SM suppressed the activating effect of oxPC in a dose-dependent manner, abolishing it almost completely at a concentration 8 times as high as that of oxPC. Thus, changes in the oxPC/SM concentration ratio in LDL may affect the regulatory mechanisms of sPLA(2)(IIA) activity in human blood, inducing stimulation or inhibition of the enzyme. Influence on regulation of sPLA(2)(IIA) activity can be useful in the development of new therapeutic approaches to the treatment of cardiovascular diseases.
Korotaeva
Aleksandra A
AA
Russian Cardiology Research Center, 3rd Cherepkovskaya Str., 15A, Moscow 121552, Russia. A.Korot@cardio.ru
Samoilova
Elena V
EV
Piksina
Galina F
GF
Prokazova
Nina V
NV
D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D054501:Group II Phospholipases A2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000737:chemistry / Q000494:pharmacology*; D013109:Sphingomyelins / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D054501:Group II Phospholipases A2