Hydrogen Peroxide Activation of Ca2+-Independent Phospholipase A2 in Uterine Stromal Cells

Birbes, Hélène; Gothié, Emmanuel; Pageaux, Jean‐François; Lagarde, Michel; Laugier, Christian

doi:10.1006/bbrc.2000.3479

Cited by 18 publications

(10 citation statements)

References 31 publications

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“…iPLA 2 involvement in oxidant-induced phospholipid hydrolysis has also been recognized to occur in uterine stromal cells (21) and, more recently, in astrocytes as well (43). 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.…”

Section: Resultsmentioning

confidence: 99%

“…Recent evidence has implicated this enzyme in the destruction of membrane phospholipid subsequent to cells entering apoptosis, resulting in the liberation of various free fatty acids to the extracellular medium (17)(18)(19). Another instance wherein iPLA 2 -mediated phospholipolysis occurs in a seemingly receptor-uncontrolled manner is during oxidative stress (20,21). Finally, cells from schizophrenic pa-tients have been reported to exhibit a constitutively elevated phospholipid fatty acid turnover, which appears to be mediated by an iPLA 2 -like activity (22).…”

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confidence: 99%

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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

Pérez

Melero

Balboa

et al. 2004

Journal of Biological Chemistry

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Group VIA calcium-independent phospholipase A 2 (iPLA 2 ) has been shown to play a major role in regulating basal phospholipid deacylation reactions in certain cell types. More recently, roles for this enzyme have also been suggested in the destruction of membrane phospholipid during apoptosis and after oxidant injury. Proposed iPLA 2 roles have rested heavily on the use of bromoenol lactone as an iPLA 2 -specific inhibitor, but this compound actually inhibits other enzymes and lipid pathways unrelated to PLA 2 , which makes it difficult to define the contribution of iPLA 2 to specific functions. In previous work, we pioneered the use of antisense technology to decrease cellular iPLA 2 activity as an alternative approach to study iPLA 2 functions. In the present study, we followed the opposite strategy and prepared U937 cells that exhibited enhanced iPLA 2 activity by stably expressing a plasmid containing iPLA 2 cDNA. Compared with control cells, the iPLA 2 -overexpressing U937 cells showed elevated responses to hydrogen peroxide with regard to both arachidonic acid mobilization and incorporation of the fatty acid into phospholipids, thus providing additional evidence for the key role that iPLA 2 plays in these events. Long-term exposure of the cells to hydrogen peroxide resulted in cell death by apoptosis, and this process was accelerated in the iPLA 2 -overexpressing cells. Increased phospholipid hydrolysis and fatty acid release also occurred in these cells. Unexpectedly, however, abrogation of U937 cell iPLA 2 activity by either methyl arachidonyl fluorophosphonate or an antisense oligonucleotide did not delay or decrease the extent of apoptosis induced by hydrogen peroxide. These results indicate that, although iPLA 2

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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

Pérez

Melero

Balboa

et al. 2004

Journal of Biological Chemistry

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“…Recent findings have suggested that ROS are a factor potentiating iPLA 2 activity. Birbes et al 9) reported that in uterine stromal cells H 2 O 2 caused a significant release of AA, which is independent of intracellular Ca 2ϩ concentration, and an increase in iPLA 2 activity, both of which are inhibited almost completely by BEL. Martínez and Moreno 10) also reported similar results that in RAW 264.7 cells and mouse peritoneal macrophages, H 2 O 2 or superoxide anion caused a marked enhancement of iPLA 2 activity in parallel with increased AA release that is sensitive to BEL.…”

Section: Regulation Of Ipla 2 Activationmentioning

confidence: 99%

Cellular Function of Calcium-Independent Phospholipase A2

Akiba

Sato

2004

Biological & Pharmaceutical Bulletin

117

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The catalytic activity of calcium-independent phospholipase A 2 (iPLA 2 ), which is classified as a group VI PLA 2 , is regulated by protein kinase C, calmodulin, and others such as reactive oxygen species. Numerous findings have shown that iPLA 2 is involved in stimulus-induced arachidonic acid release and lysophospholipid generation, although the participation is dependent upon the cell type and stimulus. The catalytic action of iPLA 2 is known to be responsible for phospholipid remodeling as a housekeeping function. However, it has been widely accepted that arachidonic acid and lysophospholipid generated by iPLA 2 act as a signaling molecule in cellular functions. Those include eicosanoid production, glucose-induced insulin secretion, Fas-induced apoptosis, cellular proliferation, membrane traffic in fusion, contribution to myocardial ischemia, and others. In this review, the functional role of iPLA 2 in cellular responses upon stimulation is the focus.

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“…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).…”

mentioning

confidence: 99%

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

Balboa

Balsinde

2002

Journal of Biological Chemistry

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Previous studies have demonstrated that U937 cells are able to mobilize arachidonic acid (AA) and synthesize prostaglandins in response to receptor-directed and soluble stimuli by a mechanism that involves the activation of Group IV cytosolic phospholipase A 2 ␣. In this paper we show that these cells also mobilize AA in response to an oxidative stress induced by H 2 O 2 through a mechanism that appears not to be mediated by cytosolic phospholipase A 2 ␣ but by the calcium-independent Group VI phospholipase A 2 (iPLA 2 ). This is supported by the following lines of evidence: (i) the response is essentially calcium-independent, (ii) it is inhibited by bromoenol lactone, and (iii) it is inhibited by an iPLA 2 antisense oligonucleotide. Enzyme assays conducted under a variety of conditions reveal that the specific activity of the iPLA 2 does not change as a result of H 2 O 2 exposure, which argues against the activation of a specific signaling cascade ending in the iPLA 2 . Rather, the oxidant acts to perturb membrane homeostasis in a way that the enzyme susceptibility/accessibility to its substrate increases, and this results in altered fatty acid release. In support of this view, not only AA, but also other fatty acids, were found to be liberated in an iPLA 2 -dependent manner in the H 2 O 2 -treated cells. Collectively, these studies underscore the importance of the iPLA 2 in modulating homeostatic fatty acid deacylation reactions and document a potentially important route under pathophysiological conditions for increasing free fatty acid levels during oxidative stress.

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Hydrogen Peroxide Activation of Ca2+-Independent Phospholipase A2 in Uterine Stromal Cells

Cited by 18 publications

References 31 publications

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

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

Cellular Function of Calcium-Independent Phospholipase A2

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

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