Role of long-chain acyl-coenzyme A synthetases in the regulation of arachidonic acid metabolism in interleukin 1尾-stimulated rat fibroblasts

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• 作者：Hiroshi Kuwata ; Makiko Yoshimura ; Yuka Sasaki ; Emiko Yoda ; Yoshihito Nakatani ; Ichiro Kudo ; Shuntaro Hara
• 关键词：AA ; arachidonic acid ; PG ; prostaglandin ; PLA2 ; phospholipase A2 ; COX ; cyclooxygenase ; ACSL ; acyl-CoA synthetase long-chain family member ; cPLA2 ; cytosolic PLA2 ; sPLA2 ; secreted PLA2 ; iPLA2 ; Ca2  ; +-independent PLA2 ; IL ; interleukin ; cPGES ; cytosolic PGE synthase ; PC ; phosphatidylcholine ; PE ; phosphatidylethanolamine ; HETE ; hydroxyeicosatetraenoic acid ; HHT ; hydroxyheptadecatrienoic acid ; AACOCF3 ; arachidonyl trifluoromethyl ketone ; ESI ; electrospray ionization ; MS ; mass spectrometry ; LC ; liqu
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：January, 2014
• 年：2014
• 卷：1841
• 期：1
• 页码：44-53
• 全文大小：854 K

文摘

Acyl coenzyme A synthetase long-chain family members (ACSLs) are a family of enzymes that convert long-chain free fatty acids into their acyl-CoAs and play an important role in fatty acid metabolism. Here we show the role of ACSL isozymes in interleukin (IL)-1尾-induced arachidonic acid (AA) metabolism in rat fibroblastic 3Y1 cells. Treatment of 3Y1 cells with triacsin C, an ACSL inhibitor, markedly enhanced the IL-1尾-induced prostaglandin (PG) biosynthesis. Small interfering RNA-mediated knockdown of endogenous Acsl4 expression increased significantly the release of AA metabolites, including PGE₂, PGD₂, and PGF_2伪, compared with replicated control cells, whereas knockdown of Acsl1 expression reduced the IL-1尾-induced release of AA metabolites. Experiments with double knockdown of Acsl4 and intracellular phospholipase A₂ (PLA₂) isozymes revealed that cytosolic PLA₂伪, but not calcium-independent PLA₂s, is involved in the Acsl4 knockdown-enhanced PG biosynthesis. Electrospray ionization mass spectrometry of cellular phospholipids bearing AA showed that the levels of some, if not all, phosphatidylcholine (PC) and phosphatidylinositol species in Acsl4 knockdown cells were decreased after IL-1尾 stimulation, while those in control cells were not so obviously decreased. In Acsl1 knockdown cells, the levels of some AA-bearing PC species were reduced even in the unstimulated condition. Collectively, these results suggest that Acsl isozymes play distinct roles in the control of AA remodeling in rat fibroblasts: Acsl4 acts as the first step of enzyme for AA remodeling following IL-1尾 stimulation, and Acsl1 is involved in the maintenance of some AA-containing PC species.