Oxidant-induced arachidonic acid release and impairment of fatty acid acylation in vascular smooth muscle cells

Abstract

Oxidative damage, which plays a major role in the early stages of atherosclerosis, is associated with arachidonic acid (AA) release in vascular smooth muscle cells (VSMC) as in other cell types. In this study, H2O2was used to investigate mechanisms of AA release from VSMC on oxidative stress. Cell treatment with H2O2inhibited AA incorporation in an inverse relationship to prolonged H2O2-induced AA release. Identical kinetics of inhibition of AA incorporation and AA release were observed after cell treatment with A[Formula: see text], a process not involving phospholipase A2(PLA2) activation as recently described (A. Cane, M. Breton, G. Béréziat, and O. Colard. Biochem. Pharmacol. 53: 327–337, 1997). AA release was not specific, since oleic acid also increased in the extracellular medium of cells treated with H2O2or A[Formula: see text] as measured by gas chromatography-mass spectrometry. In contrast, AA and oleic acid cell content decreased after cell treatment. Oleoyl and arachidonoyl acyl-CoA synthases and acyltransferases, assayed using a cell-free system, were not significantly modified. In contrast, a good correlation was observed between decreases in AA acylation and cell ATP content. The decrease in ATP content is only partially accounted for by mitochondrial damage as assayed by rhodamine 123 assay. We conclude that oxidant-induced arachidonate release results from impairment of fatty acid esterification and that ATP availability is probably responsible for free AA accumulation on oxidative stress by preventing its reesterification and/or transmembrane transport.

Role of Group VIA Calcium-independent Phospholipase A2 in Arachidonic Acid Release, Phospholipid Fatty Acid Incorporation, and Apoptosis in U937 Cells Responding to Hydrogen Peroxide

“…Interestingly, however, in cells such as alveolar macrophages (31) and vascular smooth muscle cells (32), oxidant-induced AA mobilization was found to result from impairment of fatty acid incorporation into phospholipids. Given the key role that iPLA 2 appears to play in AA deacylation/reacylation reactions in immunoinflammatory cells (7,8), it was of interest to assess the effect of H 2 O 2 on the AA incorporation mechanisms of U937 macrophage-like cells.…”

Cross-talk between Cytosolic Phospholipase A2α (cPLA2α) and Secretory Phospholipase A2 (sPLA2) in Hydrogen Peroxide-induced Arachidonic Acid Release in Murine Mesangial Cells

“…Hydrogen peroxide (H 2 O 2 ) triggers AA release and metabolism in various cell types (21)(22)(23)(24). The understanding of which forms of PLA 2 are important for AA release and how multiple forms may interact has been hampered by the fact that mammalian cells generally contain more than one form of PLA 2 .…”

Involvement of Calcium-independent Phospholipase A2in Hydrogen Peroxide-induced Accumulation of Free Fatty Acids in Human U937 Cells

“…Activation of an intracellular PLA 2 has been pointed out as the most likely mechanism for AA mobilization in vascular smooth muscle cells, stromal cells, and striatal neurons exposed to H 2 O 2 (7)(8)(9)(10)(11). In other systems however, diminished AA incorporation into phospholipids, not PLA 2 activation, has been suggested to be the event responsible for free AA accumulation (12,13). In an attempt to reconcile these conflicting results, we sought to investigate the ability of H 2 O 2 to induce AA mobilization from human monocytic U937 cells and the molecular mechanism involved in this process.…”