Phospholipase A2 enzymes differently impact PUFA release and oxylipin formation ex vivo in rat hearts. (April 2023)

• Record Type: Journal Article
• Authors: Manson, Anne; Winter, Tanja; Aukema, Harold M.
• Is Part Of: Prostaglandins, leukotrienes, and essential fatty acids. Volume 191(2023)
• Publication Date: 2023-04
• Subjects: Phospholipase A2 -- Polyunsaturated fatty acids -- Oxylipins -- Omega-3 fatty acids -- Fatty acid metabolism -- Eicosanoids; ARA arachidonic acid -- ALA α-linolenic acid -- BEL bromoenol lactone -- COX cyclooxygenase -- CT cycle threshold -- CYP cytochrome P450 -- DGLA dihomo-γ-linolenic acid -- DHA docosahexaenoic acid -- DiHDoPE dihydroxy-docosapentaenoic acid -- DiHDoHE dihydroxy-docosahexaenoic acid -- DiHETE dihydroxy-eicosatetraenoic acid -- DiHETrE dihydroxy-eicosatrienoic acid -- DiHODE dihydroxy-octadecadienoic acid -- diHOME dihydroxy-octadecenoic acid -- EPA eicosapentaenoic acid -- EpDPE epoxy-docosapentaenoic acid -- EpETrE epoxy-eicosatrienoic acid -- EpODE epoxy-octadecadienoic acid -- EpOME epoxy-octadecenoic acid -- GLA γ-linolenic acid -- HDoHE hydroxy-docosahexaenoic acid -- HEPE hydroxy-eicosapentaenoic acid -- HETE hydroxy-eicosatetraenoic acid -- HETrE hydroxy-eicosatrienoic acid -- HHTrE hydroxy-heptadecatrienoic acid -- HODE hydroxy-octadecadienoic acid -- HOTrE hydroxy-octadecatrienoic acid -- HX hepoxilin -- k keto -- LA linoleic acid -- LOX lipoxygenase -- LT leukotriene -- LX lipoxin -- MAFP methyl arachidonyl fluorophosphonate -- PAF-AH platelet-activating factor acetylhydrolase -- PG prostaglandin -- PLA2 phospholipase A2 -- PYR pyrrophenone -- triHOME trihydroxy-octadecenoic acid -- TX thromboxane -- VAR varespladib; Lipids -- Periodicals; Unsaturated fatty acids -- Periodicals; Prostaglandins -- Periodicals; Leukotrienes -- Periodicals; Fatty Acids, Unsaturated -- Periodicals; Acides gras insaturés -- Périodiques; Prostaglandines -- Périodiques; Leucotriènes -- Périodiques; Lipides -- Périodiques; 612.01577
• DOI: 10.1016/j.plefa.2023.102555
• Languages: English
• ISSNs: 0952-3278

Abstract

Highlights: sPLA2 enzymes mediate DHA release and oxylipin formation in rat hearts. iPLA2 enzymes are likely responsible for other PUFA release and oxylipin formation. COX and 12-LOX oxylipins were resistant to inhibition by PLA2 inhibitors. Oxylipin formation does not necessarily reflect PUFA release. Abstract: Phospholipase A2 (PLA2 ) enzymes cleave cell membrane phospholipids and release polyunsaturated fatty acids (PUFA), which can be converted into oxylipins. However, little is known about PLA2 preference for PUFA, and even less is known about how this further impacts oxylipin formation. Therefore, we investigated the role of different PLA2 groups in PUFA release and oxylipin formation in rat hearts. Sprague-Dawley rat heart homogenates were incubated without or with varespladib (VAR), methyl arachidonyl fluorophosphonate (MAFP) or EDTA. Free PUFA and oxylipins were determined by HPLC-MS/MS, and isoform expressions by RT-qPCR. Inhibition of sPLA2 IIA and/or V by VAR reduced the release of ARA and DHA, but only DHA oxylipins were inhibited. MAFP reduced the release of ARA, DHA, ALA, and EPA, and the formation of ARA, LA, DGLA, DHA, ALA, and EPA oxylipins. Interestingly, cyclooxygenase and 12-lipoxygenase oxylipins were not inhibited. mRNA expression levels of sPLA2 and iPLA2 isoforms were highest whereas levels of cPLA2 were low, consistent with activity. In conclusion, sPLA2 enzymes lead to the formation of DHA oxylipins, while iPLA2 is likely responsible for the formation of most other oxylipins in healthy rat hearts. Oxylipin formation cannot be implied from PUFA release, thus, both should be evaluated in PLA2 activity studies.