Cellular Arachidonate-releasing Function of Novel Classes of Secretory Phospholipase A2s (Groups III and XII)

Murakami, Makoto; Masuda, Shiro; Shimbara, Satoko; Bezzine, Sofiane; Lazdunski, M.; Lambeau, Gérard; Gelb, Michael H.; Matsukura, Satoshi; Kokubu, Fumio; Adachi, Mitsuru; Kudo, Ichiro

doi:10.1074/jbc.m211325200

Cited by 75 publications

(81 citation statements)

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“…4 and 5). Reportedly, PLA2G2F shows a ϳ2-fold preference for arachidonic acid over linoleic acid in vitro (63), and its ability to hydrolyze PC is similar to that of PLA2G3 both in vitro and in cultured cells (18). Although the pathophysiological relevance of these observations is still unclear, a recent study has shown the inducible expression of PLA2G2F (in addition to several other sPLA 2 s) in human atherosclerotic plaques (40).…”

Section: Discussionmentioning

confidence: 96%

“…The central S domain alone is sufficient for its enzymatic function (17)(18)(19). PLA2G3 undergoes proteolytic processing to produce the S domain-only form in cultured cells (19), yet it remains uncertain whether the same processing occurs in vivo.…”

mentioning

confidence: 99%

“…PLA2G3 undergoes proteolytic processing to produce the S domain-only form in cultured cells (19), yet it remains uncertain whether the same processing occurs in vivo. Forced expression of PLA2G3 in several cell types results in increased arachidonic acid metabolism, for which its potency is superior to that of PLA2G2A and next to that of PLA2G10 and PLA2G5 (18,19). PLA2G3 is immunohistochemically detected in the vascular endothelium of various tissues, alveolar epithelium and macrophages, peripheral and central nervous systems, and several types of cancer (19 -21).…”

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confidence: 99%

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Analyses of Group III Secreted Phospholipase A2 Transgenic Mice Reveal Potential Participation of This Enzyme in Plasma Lipoprotein Modification, Macrophage Foam Cell Formation, and Atherosclerosis

Sato

Kato²,

Isogai

et al. 2008

Journal of Biological Chemistry

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121

138

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Among the many mammalian secreted phospholipase A 2 (sPLA 2 ) enzymes, PLA2G3 (group III secreted phospholipase A 2 ) is unique in that it possesses unusual N-and C-terminal domains and in that its central sPLA 2 domain is homologous to bee venom PLA 2 rather than to other mammalian sPLA 2 s. To elucidate the in vivo actions of this atypical sPLA 2 , we generated transgenic (Tg) mice overexpressing human PLA2G3. Despite marked increases in PLA 2 activity and mature 18-kDa PLA2G3 protein in the circulation and tissues, PLA2G3 Tg mice displayed no apparent abnormality up to 9 months of age. However, alterations in plasma lipoproteins were observed in PLA2G3 Tg mice compared with control mice. In vitro incubation of low density (LDL) and high density (HDL) lipoproteins with several sPLA 2 s showed that phosphatidylcholine was efficiently converted to lysophosphatidylcholine by PLA2G3 as well as by PLA2G5 and PLA2G10, to a lesser extent by PLA2G2F, and only minimally by PLA2G2A and PLA2G2E. PLA2G3-modified LDL, like PLA2G5-or PLA2G10-treated LDL, facilitated the formation of foam cells from macrophages ex vivo. Accumulation of PLA2G3 was detected in the atherosclerotic lesions of humans and apoE-deficient mice. Furthermore, following an atherogenic diet, aortic atherosclerotic lesions were more severe in PLA2G3 Tg mice than in control mice on the apoE-null background, in combination with elevated plasma lysophosphatidylcholine and thromboxane A 2 levels. These results collectively suggest a potential functional link between PLA2G3 and atherosclerosis, as has recently been proposed for PLA2G5 and PLA2G10.

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Section: Discussionmentioning

confidence: 96%

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confidence: 99%

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confidence: 99%

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Analyses of Group III Secreted Phospholipase A2 Transgenic Mice Reveal Potential Participation of This Enzyme in Plasma Lipoprotein Modification, Macrophage Foam Cell Formation, and Atherosclerosis

Sato

Kato²,

Isogai

et al. 2008

Journal of Biological Chemistry

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121

138

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“…Materials-Culture of human embryonic kidney (HEK) 293 cells, human colon adenocarcinoma HCA-7 cells, human lung epithelial BEAS-2B cells, and rat fibroblastic 3Y1 cells in RPMI1640 medium (Nissui Pharmaceutical Co.) supplemented with 10% fetal calf serum was described previously (14,22,29,30). The cDNAs for human mPGES-1 (14), human COX-1 and COX-2 (4), and monkey mPGES-2 (28) were described previously.…”

Section: Methodsmentioning

confidence: 99%

Cellular Prostaglandin E2 Production by Membrane-bound Prostaglandin E Synthase-2 via Both Cyclooxygenases-1 and -2

Murakami

Nakashima

Kamei

et al. 2003

Journal of Biological Chemistry

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313

308

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Current evidence suggests that two forms of prostaglandin (PG) E synthase (PGES), cytosolic PGES and membrane-bound PGES (mPGES) -1, preferentially lie downstream of cyclooxygenase (COX) -1 and -2, respectively, in the PGE 2 biosynthetic pathway. In this study, we examined the expression and functional aspects of the third PGES enzyme, mPGES-2, in mammalian cells and tissues. mPGES-2 was synthesized as a Golgi membrane-associated protein, and spontaneous cleavage of the N-terminal hydrophobic domain led to the formation of a truncated mature protein that was distributed in the cytosol with a trend to be enriched in the perinuclear region. In several cell lines, mPGES-2 promoted PGE 2 production via both COX-1 and COX-2 in the immediate and delayed responses with modest COX-2 preference. In contrast to the marked inducibility of mPGES-1, mPGES-2 was constitutively expressed in various cells and tissues and was not increased appreciably during tissue inflammation or damage. Interestingly, a considerable elevation of mPGES-2 expression was observed in human colorectal cancer. Collectively, mPGES-2 is a unique PGES that can be coupled with both COXs and may play a role in the production of the PGE 2 involved in both tissue homeostasis and disease.Biosynthesis of prostaglandin (PG) 1 E 2 , which is produced by a variety of cells and tissues and exhibits diverse bioactivities, is mediated by three enzymatic reactions involving phospholipase A 2 (PLA 2 ), cyclooxygenase (COX), and PGE synthase (PGES). In this biosynthetic pathway, arachidonic acid (AA) released from membrane phospholipids by cytosolic or secretory PLA 2 s is converted to PGH 2 by COX-1 or COX-2 and is then isomerized to PGE 2 by terminal PGES enzymes.The constitutive COX-1 mainly promotes immediate PG production elicited by agonists promptly mobilizing intracellular Ca 2ϩ , a situation in which a burst release of AA occurs (1-5).The inducible COX-2 is essential for delayed PG generation induced by proinflammatory stimuli, during which AA is gradually supplied over long periods, and also promotes immediate PG production if it already exists in cells primed by particular stimuli (1-5). Current studies employing isozyme-specific inhibitors and knockout mice have revealed that the two COXs play distinct roles in vivo (6 -10), and segregated utilization of these enzymes at the cellular level has been explained not only by their distinct expression profiles but also by subtle differences in their AA requirement, hydroperoxide sensitivity, and subcellular localization (4, 11-13). In addition, selective coupling with various terminal PG synthases has also been shown to influence crucially the utilization of the two COX isoforms during the different phases of cell activation (14 -16). PGES enzymes, which lie downstream of COXs, occur in multiple forms in mammalian cells (1). Among them, a perinuclear membrane-bound form of PGES belonging to the MAPEG (for membrane-associated proteins involved in eicosanoid and glutathione metabolism) family, which we herein cal...

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“…On the other hand, as depicted in Figure 5, this sequence matched Group III PLA2s from the insects D. melanogaster (gi|21627771) and A. mellifera (gi|16904372), from the venom of the gila monster Heloderma suspectum (gi|104338), and from the scorpions Anuroctonus phaiodactylus (gi|46484897) and Pandinus imperator (gi|37079101), as well as a Group IX PLA2 toxin from the marine medusa Rhopilema nomadica (gi|999133). Furthermore, LOqua-PLA1 also displays homology to the carboxy domain of human Group III PLA2 (gi| 7657126) whose function is related to arachidonate release from cells (Murakami et al, 2003). At present, the substrate specificity and function for this putative secreted PLA2 is a matter of speculation, but it may be somehow involved in the hemolysis observed after envenomation (Seibert et al, 2004).…”

Section: Phospholipase A2 (Pla2)-phospholipasesmentioning

confidence: 99%

A catalog for the transcripts from the venomous structures of the caterpillar Lonomia obliqua: Identification of the proteins potentially involved in the coagulation disorder and hemorrhagic syndrome

Veiga

Ribeiro

Guimarães

et al. 2005

Gene

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Accidents with the caterpillar Lonomia obliqua are often associated with a coagulation disorder and hemorrhagic syndrome in humans. In the present study, we have constructed cDNA libraries from two venomous structures of the caterpillar, namely the tegument and the bristle. Highthroughput sequencing and bioinformatics analyses were performed in parallel. Over one thousand cDNAs were obtained and clustered to produce a database of 538 contigs and singletons (clusters) for the tegument library and 368 for the bristle library. We have thus identified dozens of fulllength cDNAs coding for proteins with sequence homology to snake venom prothrombin activator, trypsin-like enzymes, blood coagulation factors and prophenoloxidase cascade activators. We also report cDNA coding for cysteine proteases, Group III phospholipase A2, Ctype lectins, lipocalins, in addition to protease inhibitors including serpins, Kazal-type inhibitors, cystatins and trypsin inhibitor-like molecules. Antibacterial proteins and housekeeping genes are also described. A significant number of sequences were devoid of database matches, suggesting that their biologic function remains to be defined. We also report the N-terminus of the most abundant proteins present in the bristle, tegument, hemolymph, and "cryosecretion". Thus, we have created a catalog that contains the predicted molecular weight, isoelectric point, accession number, and putative function for each selected molecule from the venomous structures of L. obliqua. The role of these molecules in the coagulation disorder and hemorrhagic syndrome caused by envenomation with this caterpillar is discussed. All sequence information and the Supplemental Data, including Figures and Tables with hyperlinks to FASTA-formatted files for each contig and the best match to the Databases, are available at http://www.ncbi.nih.gov/projects/omes.

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Cellular Arachidonate-releasing Function of Novel Classes of Secretory Phospholipase A2s (Groups III and XII)

Cited by 75 publications

References 77 publications

Analyses of Group III Secreted Phospholipase A2 Transgenic Mice Reveal Potential Participation of This Enzyme in Plasma Lipoprotein Modification, Macrophage Foam Cell Formation, and Atherosclerosis

Analyses of Group III Secreted Phospholipase A2 Transgenic Mice Reveal Potential Participation of This Enzyme in Plasma Lipoprotein Modification, Macrophage Foam Cell Formation, and Atherosclerosis

Cellular Prostaglandin E2 Production by Membrane-bound Prostaglandin E Synthase-2 via Both Cyclooxygenases-1 and -2

A catalog for the transcripts from the venomous structures of the caterpillar Lonomia obliqua: Identification of the proteins potentially involved in the coagulation disorder and hemorrhagic syndrome

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