期刊
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
卷 191, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.plefa.2023.102555
关键词
PhospholipaseA2; Polyunsaturated fatty acids; Oxylipins; Omega-3 fatty acids; Fatty acid metabolism; Eicosanoids
Phospholipase A2 (PLA2) enzymes cleave cell membrane phospholipids and release polyunsaturated fatty acids (PUFA), which can be converted into oxylipins. The preference of PLA2 for different PUFA and its impact on oxylipin formation is not well understood. This study investigated the role of different PLA2 groups in PUFA release and oxylipin formation in rat hearts. The findings suggest that sPLA2 enzymes are responsible for DHA oxylipin formation, while iPLA2 is likely responsible for the formation of most other oxylipins.
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 homog-enates 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. In-hibition 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.
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