Inflammatory Activation of Arachidonic Acid Signaling in Murine P388D1 Macrophages via Sphingomyelin Synthesis

Balsinde, Jesús; Balboa, Marı́a A.; Dennis, Edward A.

doi:10.1074/jbc.272.33.20373

Cited by 65 publications

(42 citation statements)

References 45 publications

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“…Thus the data suggest that lipid hydrolysis by iPLA 2 occurs more readily in H 2 O 2 -treated cells because of changes in the physical state of membrane substrates, which may result, at least in part, from lipid peroxide accumulation. How this facilitated catalysis occurs is presently unknown, but a number of factors that alter membrane lipid packing are well documented to increase fatty acid release both in vitro and in vivo (34).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Proinflammatory stimuli may cause alterations in membrane lipid packing and asymmetry, which are thought to induce increased cellular sPLA 2 -IIA sensitivity. More recently, sphingomyelin turnover, one of the primary responses following ligation of the receptors for proinflammatory cytokines (67,68), has been proposed to perturb the outer leaflet of the membrane, thereby modulating the activity of sPLA 2 s acting on biological membranes (69,70).…”

Section: Discussionmentioning

confidence: 99%

The Functions of Five Distinct Mammalian Phospholipase A2s in Regulating Arachidonic Acid Release

Murakami¹,

Shimbara²,

Kambe³

et al. 1998

Journal of Biological Chemistry

352

267

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“…Moreover, LPS and platelet-activating factor-induced sphingomyelin synthesis is dependent on group V PLA 2 in the latter cells (9).…”

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confidence: 99%

Bactericidal Properties of Group IIA and Group V Phospholipases A2

Grönroos

Laine

Janssen

et al. 2001

The Journal of Immunology

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Group V phospholipase A2 (PLA2) is a recently characterized 14-kDa secretory PLA2 of mammalian heart and macrophage-derived cells. Group IIA PLA2, which is structurally close to group V PLA2, has been shown to kill Gram-positive bacteria in vitro and to prevent symptoms of Gram-positive infection in vivo. We studied the antibacterial properties of fully active recombinant rat group IIA and V PLA2s. Both group IIA and V PLA2s were highly bactericidal against Gram-positive bacteria, including methicillin-resistant staphylococci and vancomycin-resistant enterococci. Only high concentrations of group IIA PLA2 showed some bactericidal effect against the Gram-negative bacterium Escherichia coli. Our results confirm that group IIA PLA2 is a potent antibacterial enzyme against Gram-positive bacteria. Moreover, we show here that group V PLA2 is a novel antibacterial mammalian protein, but is less potent than group IIA PLA2. Both enzymes may be considered as future therapeutic agents against bacterial infections.

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Inflammatory Activation of Arachidonic Acid Signaling in Murine P388D1 Macrophages via Sphingomyelin Synthesis

Cited by 65 publications

References 45 publications

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

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

The Functions of Five Distinct Mammalian Phospholipase A2s in Regulating Arachidonic Acid Release

Bactericidal Properties of Group IIA and Group V Phospholipases A2

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