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Hydrolysis of glycerophosphocholine epoxides by human group IIA , V, and X secretory phospholipases A 2
Author(s) -
Kuksis Arnis,
Pruzanski Waldemar
Publication year - 2021
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1002/lipd.12320
Subject(s) - chemistry , hydrolysis , docosahexaenoic acid , eicosapentaenoic acid , phosphatidylcholine , phospholipid , arachidonic acid , chromatography , biochemistry , fatty acid , polyunsaturated fatty acid , enzyme , membrane
This study was prompted by recent reports that epoxyeicosatrienoic (EET) and epoxyeicosatetraenoic (EEQ) acids accelerate tumor growth and metastasis by stimulation of angiogenesis, while eicosapentaenoic (EPA) and epoxydocosapentaenoic (EDP) acids inhibit angiogenesis, tumor growth, and metastasis. Cytochrome P450 epoxygenases convert arachidonic to EET, eicosapentaenoic acid to EEQ, and docosahexaenoic acid to EDP, which are found both in free form and esterified to glycerophosphocholine (GPC). Both free and esterified epoxy (EP) acids are also formed during lipid autoxidation. For biological activity, the GPC‐EP requires hydrolysis, which we presumed could occur by sPLA 2 s located in proximity of lipoproteins carrying the lipid epoxides. The plasma lipoproteins were isolated by ultracentrifugation and analyzed by LC/ESI‐MS. The GPC‐EPs were identified by reference to standards and to retention times of phospholipid masses. The GPC‐EP monoepoxides (corrected for isobaric ether overlaps) in stored human LDL, HDL, HDL 3 , or APHDL ranged from 0 to 1 nmol/mg protein, but during 4‐h incubation at 37°C increased to 1–5 nmol/mg protein. An incubation of autoxidized LDL, HDL, or HDL 3 with 1 μg/ml of group V or X sPLA 2 resulted in complete hydrolysis of diacyl GPC epoxide esters. Group IIA sPLA 2 at 1 μg/ml failed to produce significant hydrolysis in 4 h, but at 2.5 μg/ml in 8 h yielded almost 80% hydrolysis, which represented complete diacyl GPC‐EP hydrolysis. The present study shows that group IIA, V, and X sPLA 2 s are capable of extensive hydrolysis of PtdCho epoxides of autoxidized plasma lipoproteins. Therefore, all three human sPLA 2 s were potentially capable of inducing epoxide biological activity in vivo .