論文 - 詳細
| RRC ID | 39133 |
|---|---|
| 著者 | Murakami M, Shimbara S, Kambe T, Kuwata H, Winstead MV, Tischfield JA, Kudo I. |
| タイトル | The functions of five distinct mammalian phospholipase A2S in regulating arachidonic acid release. Type IIa and type V secretory phospholipase A2S are functionally redundant and act in concert with cytosolic phospholipase A2. |
| ジャーナル | J Biol Chem |
| Abstract |
We examined the relative contributions of five distinct mammalian phospholipase A2 (PLA2) enzymes (cytosolic PLA2 (cPLA2; type IV), secretory PLA2s (sPLA2s; types IIA, V, and IIC), and Ca2+-independent PLA2 (iPLA2; type VI)) to arachidonic acid (AA) metabolism by overexpressing them in human embryonic kidney 293 fibroblasts and Chinese hamster ovary cells. Analyses using these transfectants revealed that cPLA2 was a prerequisite for both the calcium ionophore-stimulated immediate and the interleukin (IL)-1- and serum-induced delayed phases of AA release. Type IIA sPLA2 (sPLA2-IIA) mediated delayed AA release and, when expressed in larger amounts, also participated in immediate AA release. sPLA2-V, but not sPLA2-IIC, behaved in a manner similar to sPLA2-IIA. Both sPLA2s-IIA and -V, but not sPLA2-IIC, were heparin-binding PLA2s that exhibited significant affinity for cell-surface proteoglycans, and site-directed mutations in residues responsible for their membrane association or catalytic activity markedly reduced their ability to release AA from activated cells. Pharmacological studies using selective inhibitors as well as co-expression experiments supported the proposal that cPLA2 is crucial for these sPLA2s to act properly. The AA-releasing effects of these sPLA2s were independent of the expression of the M-type sPLA2 receptor. Both cPLA2, sPLA2s-IIA, and -V were able to supply AA to downstream cyclooxygenase-2 for IL-1-induced prostaglandin E2 biosynthesis. iPLA2 increased the spontaneous release of fatty acids, and this was further augmented by serum but not by IL-1. Finally, iPLA2-derived AA was not metabolized to prostaglandin E2. These observations provide evidence for the functional cross-talk or segregation of distinct PLA2s in mammalian cells in regulating AA metabolism and phospholipid turnover. |
| 巻・号 | 273(23) |
| ページ | 14411-23 |
| 公開日 | 1998-6-5 |
| DOI | 10.1074/jbc.273.23.14411 |
| PII | S0021-9258(19)77486-9 |
| PMID | 9603953 |
| MeSH | Animals Arachidonic Acid / metabolism* CHO Cells Calcimycin / pharmacology Cells, Cultured Cricetinae Cyclooxygenase 2 Dinoprostone / biosynthesis Enzyme Inhibitors / pharmacology Fatty Acids / metabolism Gene Expression / genetics Heparin / metabolism Humans Interleukin-1 / pharmacology Isoenzymes / metabolism Kidney / embryology Mammals Membrane Proteins Mutagenesis, Site-Directed / genetics Phospholipases A / chemistry Phospholipases A / physiology* Phospholipases A2 Phospholipids / metabolism Prostaglandin-Endoperoxide Synthases / metabolism Sequence Alignment Transfection / genetics |
| IF | 4.238 |
| 引用数 | 318 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | CHO-K1(RCB0285) |