1993 Fiscal Year Annual Research Report

生理活性脂質の生合成酵素と受容体の遺伝子発現に関する研究

Research Project

Project/Area Number	05304027
Research Institution	Kyoto University
Principal Investigator	市川厚京都大学, 薬学部, 教授 (10025695)
Co-Investigator(Kenkyū-buntansha)	成宮周京都大学, 医学部, 教授 (70144350) 清水孝雄東京大学, 医学部, 教授 (80127092) 須田立雄昭和大学, 歯学部, 教授 (90014034) 岡本光弘大阪大学, 医学部, 教授 (90028613) 井上圭三東京大学, 薬学部, 教授 (30072937)
Keywords	アラキドン酸 / プロスタグランジン / PAF / ステロイド産生 / レチノイン酸 / ホスホリパーゼA_2 / リポキシゲナーゼ
Research Abstract	[I]生合成酵素の発現とその調節の分子機構 (1)(井上)II型ホスホリパーゼA_2に炎症時に誘導される新規のCa^<2+>とアラキドン酸含有リン脂質に特異的な60kDa分子種を発見した。(2)(吉本)ブタ白血球アラキドン酸12-リポキシゲナーゼの触媒機能を営む構造を部位特異的変異により解析した。(3)(岡本)遺伝性のNa^+負荷誘引高血圧ラットの副腎からP-450(11β)cDNAをクローニングして、その構造を決定した結果、Na^+感受性ラットは野生型のそれと同じ構造であったが、Na^+耐性ラットの酵素に変異を発見した。 (4)(諸橋)ステロイド産生細胞に特異的に発現する転写因子Ad4BPを非産生細胞で発現させることに成功し、それによるP450遺伝子の転写活性化を解析した。(5)(石村)副腎皮質の束状層に特異的な糖質コルチコイド合成酵素遺伝子の5'側上流に発現に重要な配列を発見し、その結合蛋白を同定した。(6)(須田)腎臓におけるビタミンD-24-水酸化酵素の常時誘導は腎で合成される1α,25(OH)2D_3によるautocrine/paracrine機構によることを解明した。 [II]受容体の分子構造と機能、および遺伝子の発現機構 (7)(市川)マウスPGE受容体のサブタイプEP1,EP2,EP3の遺伝子cDNAのクローニングを行った。また、PGJ_2が血管内皮細胞においてヘムオキシゲナーゼを誘導すること、この遺伝子プロモータ領域を解析し、PGJ_2の特異的プロモータ部位の存在とそれに働くトランス因子の存在を見いだした。 (8)(成宮)ウシ副腎PGE受容体EP3のcDNAクローニングを行った結果、EP3mRNAがスプライシングを受けC末端の異なる4つのイソフォームを産生することを発見した。また、これらは異なる情報伝達を行う。さらに、ヒトTXA_2受容体遺伝子のクローニングを行った。(9)(清水)ヒトPAF受容体の遺伝子のmRNAには二種類存在し、各々は異なるプロモータ制御を受けていることを発見した。さらに、PAF受容体刺激はMAPキナーゼ系と共役することを明らかにした。(10)(村松)レチノイン酸応答性の成長因子ミッドカインのプロモータを解析し、レチノイン酸応答エレメントを同定した。

Research Products
(29 results)

All Other

All Publications (29 results)

[Publications] Honda Akiko: "Cloning and expression of a cDNA for mouse prostaglandin E receptor EP_2 subtype" The Journal of Biological Chemistry. 268. 7759-7762 (1993)
[Publications] Watabe Akiko: "Cloning and expression of cDNA for a mouse EP_1 subtype of prostaglandin E receptor" The Journal of Biological Chemistry. 268. 20175-20178 (1993)
[Publications] Koizumi Tomonobu: "Activation of heat shock transcription factors by ^<12>-prostaglandin J_2 and its inhibition by intracellular glutathione" Biochemical Pharmacology. 45. 2457-2464 (1993)
[Publications] Murakami,M.,: "Triggering of degranulation in mast cells by exogenous type II phospholipase A_2" J.Immunol.151. 5675-5684 (1993)
[Publications] Fujimori,Y.: "Characteristics of lysophospholipase activity expressed by cytosolic phospholipase A_2" Eur.J.Biochem.218. 629-635 (1993)
[Publications] Uehara,Y.: "De novo synthesis of phospholipase A_2 and prostacyclin production by proliferating rat smooth muscle cells" Prostaglandins. 46. 331-346 (1993)
[Publications] Nomura Masatoshi: "Three forms of rat CYP11β genes;11β-hydroxylase,aldosterone synthase,and a novel gene" J.Biochem.113. 144-152 (1993)
[Publications] Honda Shin-ichiro: "Ad4BP regulating steroidogenic P-450 gene is a member of steroid hormone receptor superfamily." The Journal of Biological Chemistry. 268. 7494-7502 (1993)
[Publications] Morohashi Ken-ichiro: "Activation of CYP11A and CYP11B gene promoters by the steroidogenic cell-specific transcription factor,Ad4BP" Mol.Endocrinol.7. 1196-1204 (1993)
[Publications] Mukai: "Isolation and characterization of rat CYP11β genes in late steps of mineralo- and glucocorticoid syntheses" The Journal of Biological Chemistry. 268. 9130-9137 (1993)
[Publications] Mitani: "A novel cell layer without corticosteroid synthesizing enzymes in rat adrenal cortex:histochemical detection and possible---" Endocrinology. (in press). (1994)
[Publications] 石村巽: "副腎皮質ホルモン生合成の酵素" 最新内科学大系. 15. 15-27 (1993)
[Publications] Mahmud,I.: "Induction of cyclooxygenase and suppression of 12-lipoxygenase in human erythroleukemia cells upon phorbol ester-induced---" Biochimica Biophysica Acta. 1166. 211-216 (1993)
[Publications] Chang,W.-C.: "Induction of arachidonate 12-lipoxygenase mRNA by epidermal growth factor in A431 cells" The Journal of Biological Chemistry. 268. 18734-18739 (1993)
[Publications] Suzuki,H.: "Site-directed mutagenesis analysis of arachidonate 12-lipoxygenase of porcine leukocytes" Biochimica et Biophysica Acta. (in press). (1994)
[Publications] Matsukawa,N.: "Dahl's salt-resistant normotensive rat has mutations in cytochrome P450(11β)" The Journal of Biological Chemistry. 268. 9117-9121 (1993)
[Publications] Nomura,M.: "Three forms of rat CYP11β genes" J.Biochem.113. 144-152 (1993)
[Publications] Okamoto,M.: "Regulation of steroid 11β/18 hydroxylation" Progress in Endocrinology. (in press). (1994)
[Publications] Namba,T: "Alternative splicing of C-terminal tail of prostaglandin E receptor subtype EP_3 determines G-protein specificity" Nature. 365. 166-170 (1993)
[Publications] Ushikubi,F.: "Thromboxane-A_2 receptor is highly expressed in mouse immature thymocytes and mediates DNA fragmentation and apoptosis" Journal of experimental Medicine. 178. 1825-1830 (1993)
[Publications] Nusing,RM.: "Characterization and chromosomal mapping of the human thromboxane-A_2 receptor gene" The Journal of Biological Chemistry. 268. 25253-25259 (1993)
[Publications] Muramatsu,H.: "Midkine(MK),a retinoic acid-inducible growth/differentiation factor:immunochemical evidence for the function and distribution" Dev.Biol.159. 392-402 (1993)
[Publications] Satoh,J.: "Midkine that promotes survival of human neurons is produced by fetal human astrocytes in culture" Dev.Brain Res.75. 201-205 (1993)
[Publications] Matsubara,S.: "Mapping and characterization of retino c acid-responsive enhancer of midkine,a novel heparin binding growth/---" J.Biochem.(in press). (1994)
[Publications] Suda Tatsuo: "The mechanisms of regulation of vitamine D metabolism in the kidney" Current Opinion in Nephology and Hypertension. 3(in press). (1994)
[Publications] Nishimura Atsushi: "Regulation of in RNA expression of 1α,25-dihydroxyvitamin D_3-24-hydroxylase in rat osteoblasts." Endocrinology. 134(in press). (1994)
[Publications] Yokomizo: "Enzymatic inactivation of leukotriene B_4 by a novel enzyme found in the porcine kidney" The Journal of Biological Chemistry. 268. 18128-18135 (1993)
[Publications] Mutoh: "Two different promoters direct expression of two distinct forms of mRNAs of human PAF receptor" FEBS Lett.322. 129-134 (1993)
[Publications] Mori: "Energy-dependent export of leukotriene B_4 in Xenopus oocytes" Biochimica et Biophysica Acta. 1168. 23-29 (1993)

1993 Fiscal Year Annual Research Report

生理活性脂質の生合成酵素と受容体の遺伝子発現に関する研究

Principal Investigator

市川 厚 京都大学, 薬学部, 教授 (10025695)

Research Products

[Publications] Honda Akiko: "Cloning and expression of a cDNA for mouse prostaglandin E receptor EP_2 subtype" The Journal of Biological Chemistry. 268. 7759-7762 (1993)

[Publications] Watabe Akiko: "Cloning and expression of cDNA for a mouse EP_1 subtype of prostaglandin E receptor" The Journal of Biological Chemistry. 268. 20175-20178 (1993)

[Publications] Koizumi Tomonobu: "Activation of heat shock transcription factors by ^<12>-prostaglandin J_2 and its inhibition by intracellular glutathione" Biochemical Pharmacology. 45. 2457-2464 (1993)

[Publications] Murakami,M.,: "Triggering of degranulation in mast cells by exogenous type II phospholipase A_2" J.Immunol.151. 5675-5684 (1993)

[Publications] Fujimori,Y.: "Characteristics of lysophospholipase activity expressed by cytosolic phospholipase A_2" Eur.J.Biochem.218. 629-635 (1993)

[Publications] Uehara,Y.: "De novo synthesis of phospholipase A_2 and prostacyclin production by proliferating rat smooth muscle cells" Prostaglandins. 46. 331-346 (1993)

[Publications] Nomura Masatoshi: "Three forms of rat CYP11β genes;11β-hydroxylase,aldosterone synthase,and a novel gene" J.Biochem.113. 144-152 (1993)

[Publications] Honda Shin-ichiro: "Ad4BP regulating steroidogenic P-450 gene is a member of steroid hormone receptor superfamily." The Journal of Biological Chemistry. 268. 7494-7502 (1993)

[Publications] Morohashi Ken-ichiro: "Activation of CYP11A and CYP11B gene promoters by the steroidogenic cell-specific transcription factor,Ad4BP" Mol.Endocrinol.7. 1196-1204 (1993)

[Publications] Mukai: "Isolation and characterization of rat CYP11β genes in late steps of mineralo- and glucocorticoid syntheses" The Journal of Biological Chemistry. 268. 9130-9137 (1993)

[Publications] Mitani: "A novel cell layer without corticosteroid synthesizing enzymes in rat adrenal cortex:histochemical detection and possible---" Endocrinology. (in press). (1994)

[Publications] 石村 巽: "副腎皮質ホルモン生合成の酵素" 最新内科学大系. 15. 15-27 (1993)

[Publications] Mahmud,I.: "Induction of cyclooxygenase and suppression of 12-lipoxygenase in human erythroleukemia cells upon phorbol ester-induced---" Biochimica Biophysica Acta. 1166. 211-216 (1993)

[Publications] Chang,W.-C.: "Induction of arachidonate 12-lipoxygenase mRNA by epidermal growth factor in A431 cells" The Journal of Biological Chemistry. 268. 18734-18739 (1993)

[Publications] Suzuki,H.: "Site-directed mutagenesis analysis of arachidonate 12-lipoxygenase of porcine leukocytes" Biochimica et Biophysica Acta. (in press). (1994)

[Publications] Matsukawa,N.: "Dahl's salt-resistant normotensive rat has mutations in cytochrome P450(11β)" The Journal of Biological Chemistry. 268. 9117-9121 (1993)

[Publications] Nomura,M.: "Three forms of rat CYP11β genes" J.Biochem.113. 144-152 (1993)

[Publications] Okamoto,M.: "Regulation of steroid 11β/18 hydroxylation" Progress in Endocrinology. (in press). (1994)

[Publications] Namba,T: "Alternative splicing of C-terminal tail of prostaglandin E receptor subtype EP_3 determines G-protein specificity" Nature. 365. 166-170 (1993)

[Publications] Ushikubi,F.: "Thromboxane-A_2 receptor is highly expressed in mouse immature thymocytes and mediates DNA fragmentation and apoptosis" Journal of experimental Medicine. 178. 1825-1830 (1993)

[Publications] Nusing,RM.: "Characterization and chromosomal mapping of the human thromboxane-A_2 receptor gene" The Journal of Biological Chemistry. 268. 25253-25259 (1993)

[Publications] Muramatsu,H.: "Midkine(MK),a retinoic acid-inducible growth/differentiation factor:immunochemical evidence for the function and distribution" Dev.Biol.159. 392-402 (1993)

[Publications] Satoh,J.: "Midkine that promotes survival of human neurons is produced by fetal human astrocytes in culture" Dev.Brain Res.75. 201-205 (1993)

[Publications] Matsubara,S.: "Mapping and characterization of retino c acid-responsive enhancer of midkine,a novel heparin binding growth/---" J.Biochem.(in press). (1994)

[Publications] Suda Tatsuo: "The mechanisms of regulation of vitamine D metabolism in the kidney" Current Opinion in Nephology and Hypertension. 3(in press). (1994)

[Publications] Nishimura Atsushi: "Regulation of in RNA expression of 1α,25-dihydroxyvitamin D_3-24-hydroxylase in rat osteoblasts." Endocrinology. 134(in press). (1994)

[Publications] Yokomizo: "Enzymatic inactivation of leukotriene B_4 by a novel enzyme found in the porcine kidney" The Journal of Biological Chemistry. 268. 18128-18135 (1993)

[Publications] Mutoh: "Two different promoters direct expression of two distinct forms of mRNAs of human PAF receptor" FEBS Lett.322. 129-134 (1993)

[Publications] Mori: "Energy-dependent export of leukotriene B_4 in Xenopus oocytes" Biochimica et Biophysica Acta. 1168. 23-29 (1993)

市川厚京都大学, 薬学部, 教授 (10025695)

[Publications] 石村巽: "副腎皮質ホルモン生合成の酵素" 最新内科学大系. 15. 15-27 (1993)