Cellular Distribution, Post-translational Modification, and Tumorigenic Potential of Human Group III Secreted Phospholipase A2

Murakami, Makoto; Masuda, Shiro; Shimbara, Satoko; Ishikawa, Yukio; Ishii, Toshiharu; Kudo, Ichiro

doi:10.1074/jbc.m502088200

Cited by 74 publications

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“…The cell type was identified by conventional hematoxylin and eosin staining of serial sections adjacent to the specimen used for immunohistochemistry. Rabbit antisera for human and mouse PLA2G2A, PLA2G5, and PLA2G10 have been described previously (15,19). Immunostaining for human ␣-smooth muscle actin (SMA) (clone 1A4; Dako Cytomation) and human macrophages (clone HAM56; Dako Cytomation) was also performed using the EnVisionϩ kit (Dako Cytomation) for identification of smooth muscle cells and monocytes/ macrophages, respectively (40).…”

Section: Methodsmentioning

confidence: 99%

“…Histochemistry-Immunohistochemistry of mouse and human tissue sections was performed as described previously (19). Use of human tissues was approved by the ethics committee of our faculty.…”

Section: Methodsmentioning

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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confidence: 99%

“…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. 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).…”

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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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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: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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