シクロオキシゲナーゼ-2のヒト遺伝子構造と発現
種々のプロスタグランジン(PG)は, 疼痛, 発熱をはじめさまざまな炎症反応のメディエーターとして働く. その生合成は, アラキドン酸からPGG2を生成するシクロオキシゲナーゼ反応と, PGG2からPGH2を生成するヒドロペルオキシダーゼ反応の二つの反応を触媒する二機能性酵素, PGエンドペルオキシド合成酵素(EC1. 14. 99. 1, 一般には簡略化してたんにシクロオキシゲナーゼとよばれる場合が多い. 以下, 本稿では, COXと略記することにする)により制御されている. 非ステロイド性抗炎症薬(NSAID)の多くは, この酵素のシクロオキシゲナーゼ活性を阻害しPG産生を抑制することによ...
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| Published in | 炎症 Vol. 15; no. 4; pp. 283 - 292 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本炎症・再生医学会
10.07.1995
日本炎症学会 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0389-4290 1884-4006 |
| DOI | 10.2492/jsir1981.15.283 |
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| Abstract | 種々のプロスタグランジン(PG)は, 疼痛, 発熱をはじめさまざまな炎症反応のメディエーターとして働く. その生合成は, アラキドン酸からPGG2を生成するシクロオキシゲナーゼ反応と, PGG2からPGH2を生成するヒドロペルオキシダーゼ反応の二つの反応を触媒する二機能性酵素, PGエンドペルオキシド合成酵素(EC1. 14. 99. 1, 一般には簡略化してたんにシクロオキシゲナーゼとよばれる場合が多い. 以下, 本稿では, COXと略記することにする)により制御されている. 非ステロイド性抗炎症薬(NSAID)の多くは, この酵素のシクロオキシゲナーゼ活性を阻害しPG産生を抑制することにより治療効果を発揮するが, 同時に胃潰瘍や腎障害などの副作用を引き起こすことも知られている. 最近, COXの新しいアイソザイムとしてCOX-2が見出され, COXには少なくとも2種類のアイソザイムが存在することが明らかとなった. 以前より研究されてきたCOX-1が, 胃や腎をはじめさまざまな組織に構成的に発現しているのに対し, COX-2は炎症性刺激などに応じて短時間に誘導され, COX-1と明らかに異なる発現パターンを示す. |
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| AbstractList | 種々のプロスタグランジン(PG)は, 疼痛, 発熱をはじめさまざまな炎症反応のメディエーターとして働く. その生合成は, アラキドン酸からPGG2を生成するシクロオキシゲナーゼ反応と, PGG2からPGH2を生成するヒドロペルオキシダーゼ反応の二つの反応を触媒する二機能性酵素, PGエンドペルオキシド合成酵素(EC1. 14. 99. 1, 一般には簡略化してたんにシクロオキシゲナーゼとよばれる場合が多い. 以下, 本稿では, COXと略記することにする)により制御されている. 非ステロイド性抗炎症薬(NSAID)の多くは, この酵素のシクロオキシゲナーゼ活性を阻害しPG産生を抑制することにより治療効果を発揮するが, 同時に胃潰瘍や腎障害などの副作用を引き起こすことも知られている. 最近, COXの新しいアイソザイムとしてCOX-2が見出され, COXには少なくとも2種類のアイソザイムが存在することが明らかとなった. 以前より研究されてきたCOX-1が, 胃や腎をはじめさまざまな組織に構成的に発現しているのに対し, COX-2は炎症性刺激などに応じて短時間に誘導され, COX-1と明らかに異なる発現パターンを示す. |
| Author | 原, 俊太郎 七山, 豊通 田辺, 忠 |
| Author_FL | NANAYAMA Toyomichi HARA Shuntaro TANABE Tadashi |
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| Copyright | 日本炎症･再生医学会 |
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| DocumentTitleAlternate | Structure and expression of the human cyclooxygenase-2 gene |
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| References_xml | – reference: 40) Wimsatt, J., Nathanielsz, P. W., Sirois, J.: Induction of prostaglandin endoperoxide synthase isoform-2 in ovine cotyledonary tissues during late gestation. Endocrinology 133: 1068-1073, 1993. – reference: 49) Hempel, S. L., Monick, M. M., He, B., Yano, T., Hunninghake, G. W.: Synthesis of prostaglandin H synthase-2 by human alveolar macrophages in response to lipopolysaccharide is inhibited by decreased cell oxidant tone. J. Biol. Chem. 269: 32979-32984, 1994. – reference: 63) 井上裕康, 横山知永子, 田辺忠: 新しい誘導型シクロオキシゲナーゼ-遺伝子構造と発現調節機構を中心として-蛋白質核酸酵素 40: 399-408, 1995. – reference: 20) O'Sullivan, M. G., Chilton, F. H., Huggins, Jr., E. M., McCall, C. E.: Lipopolysaccharide priming of alveolar macrophages for enhanced synthesis of prostanoids involves induction of a novel prostaglandin H synthase. J. Biol. Chem. 267: 14547-14550, 1992. – reference: 10) O'Banion, M. K., Winn, V. D., Young, D. A.: cDNA cloning and functional activity of a glucocorticoidregulated inflammatory cyclooxygenase. Proc. Natl. Acad. Sci. USA 89: 4888-4892, 1992. – reference: 34) 小友進, 樋口昭平, 二木伸子: COX-2を選択的に抑制する抗炎症薬炎症と免疫3: 29-36, 1995 – reference: 12) Feng, L., Sun, W., Xia, Y., Tang, W. W., Chanmugam, P. et al.: Cloning two isoforms of rat cyclooxygenase : differential regulation of their expression. Arch. Biochem. Biophys. 307 : 361-368, 1993. – reference: 36) O'Neill, G. P., Ford-Hutchinson, A. W.: Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett. 330: 156-160, 1993. – reference: 17) Sirois, J., Richards, J. S.: Purification and characterization of a novel, distinct isoform of prostaglandin endoperoxide synthase induced by human chorionic gonadotropin in granulosa cells of rat preovulatory follicles. J. Biol. Chem. 267: 6382-6388, 1992. – reference: 59) DeWitt, D. L., Meade, E. A.: Serum and glucocorticoid regulation of gene transcription and expression of the prostaglandin H synthase-1 and prostaglandin H synthase-2 isozymes. Arch. Biochem. Biophys. 306: 94-102, 1993. – reference: 61) Herschman, H. R.: Regulation of prostaglandin synthase-1 and prostaglandin synthase-2. Cancer Metastasis Rev. 13 : 241-256, 1994. – reference: 53) Inoue, H., Nanayama, T., Hara, S., Yokoyama, C., Tanabe, T.: The cyclic AMP response element plays an essential role in the expression of the human prostaglandin-endoperoxide synthase 2 gene in differentiated U937 monocytic cells. FEBS Lett. 350: 51-54, 1994. – reference: 38) Sirois, J., Simmons, D. L., Richards, J. A.: Hormonal regulation of messenger ribonucleic acid encoding a novel isof orm of prostaglandin endoperoxide H synthase in rat preovulatory follicles: induction in vivo and in vitro. J. Biol. Chem. 267: 11586-11592, 1992. – reference: 48) Takahashi, Y., Taketani, Y., Endo, T., Yamamoto, S., Kumegawa, M.: Studies on the induction of cyclooxygenase isozymes by various prostaglandins in mouse osteoblastic cell line with reference to signal transduction pathways. Biochim. Biophys. Acta 1212: 217-224, 1994. – reference: 22) Hempel, S. L., Monick, M. M., Hunninghake, G.W.: Lipopolysaccharide induces prostaglandin H synthase-2 protein and mRNA in human alveolar macrophages and blood monocytes. J. Clin. Invest. 93 : 391-396, 1994. – reference: 2) Rosen, G. D., Birkenmeier, T. M., Raz, A., Holtzman, W. I.: Identification of a cyclooxygenaserelated gene and its potential role in prostaglandin formation. Biochem. Biophys. Res. 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| Snippet | 種々のプロスタグランジン(PG)は, 疼痛, 発熱をはじめさまざまな炎症反応のメディエーターとして働く. その生合成は, アラキドン酸からPGG2を生成するシクロオキシゲナーゼ反応と, PGG2からPGH2を生成するヒドロペルオキシダーゼ反応の二つの反応を触媒する二機能性酵素,... |
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| SubjectTerms | COX-2 cyclooxygenase gene expression gene structure prostaglandin endoperoxide synthase |
| Title | シクロオキシゲナーゼ-2のヒト遺伝子構造と発現 |
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