Journal
LIPIDS
Volume 56, Issue 5, Pages 521-535Publisher
WILEY
DOI: 10.1002/lipd.12320
Keywords
epoxides; GPC-EP; in vitro hydrolysis; LC; ESI-MS; plasma lipoproteins; secretory PLA2
Funding
- Donnelly Center, University of Toronto
- R. E. Court and Co
Ask authors/readers for more resources
This study explores the effects of epoxyeicosatrienoic (EET) and epoxyeicosatetraenoic (EEQ) acids on tumor growth and metastasis, as well as the inhibitory effects of eicosapentaenoic (EPA) and epoxydocosapentaenoic (EDP) acids. It also investigates the conversion of precursor fatty acids to epoxy acids by cytochrome P450 epoxygenases, and the formation of epoxy acids during lipid autoxidation.
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, HDL3, or APHDL ranged from 0 to 1 nmol/mg protein, but during 4-h incubation at 37 degrees C increased to 1-5 nmol/mg protein. An incubation of autoxidized LDL, HDL, or HDL3 with 1 mu g/ml of group V or X sPLA(2) resulted in complete hydrolysis of diacyl GPC epoxide esters. Group IIA sPLA(2) at 1 mu g/ml failed to produce significant hydrolysis in 4 h, but at 2.5 mu g/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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available