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 sPLA₂s 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, HDL₃, 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 HDL₃ with 1 μg/ml of group V or X sPLA₂ resulted in complete hydrolysis of diacyl GPC epoxide esters. Group IIA sPLA₂ 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 sPLA₂s are capable of extensive hydrolysis of PtdCho epoxides of autoxidized plasma lipoproteins. Therefore, all three human sPLA₂s were potentially capable of inducing epoxide biological activity in vivo.

中文翻译：

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人组 IIA、V 和 X 分泌型磷脂酶 A2 水解甘油磷酸胆碱环氧化物

这项研究是由最近的报道推动的，即环氧二十碳三烯酸 (EET) 和环氧二十碳四烯酸 (EEQ) 酸通过刺激血管生成来加速肿瘤生长和转移，而二十碳五烯酸 (EPA) 和环氧二十碳五烯酸 (EDP) 酸抑制血管生成、肿瘤生长和转移。细胞色素 P450 环氧合酶将花生四烯酸转化为 EET，将二十碳五烯酸转化为 EEQ，将二十二碳六烯酸转化为 EDP，这些物质以游离形式和酯化为甘油磷酸胆碱 (GPC)。在脂质自氧化过程中也会形成游离和酯化的环氧 (EP) 酸。对于生物活性，GPC-EP 需要水解，我们推测 sPLA _{2可能会发生水解}s位于携带脂质环氧化物的脂蛋白附近。通过超速离心分离血浆脂蛋白并通过LC/ESI-MS分析。通过参考标准和磷脂质量的保留时间来鉴定 GPC-EP。_{储存的人 LDL、HDL、HDL 3}或 APHDL中的 GPC-EP 单环氧化物（校正同量异位醚重叠）的范围为 0 至 1 nmol/mg 蛋白质，但在 37°C 孵育 4 小时期间增加到 1-5 nmol /毫克蛋白质。自氧化的 LDL、HDL 或 HDL ₃与 1 μg/ml V 组或 X 组 sPLA ₂一起温育导致二酰基 GPC 环氧化物酯完全水解。IIA 组 sPLA ₂在 1 μg/ml 下 4 小时内未能产生显着水解，但在 2.5 μg/ml 下 8 小时内产生几乎 80% 的水解，这代表完全的二酰基 GPC-EP 水解。本研究表明 IIA、V 和 X 组 sPLA ₂ s 能够广泛水解自氧化血浆脂蛋白的 PtdCho 环氧化物。因此，所有三种人类 sPLA ₂ s 都可能在体内诱导环氧化物生物活性。