1994 Fiscal Year Annual Research Report

新しい細胞内情報伝達物質サイクリックADP-リボースの合成酵素と受容体の解明

Research Project

Project/Area Number	05404018
Research Institution	Tohoku University
Principal Investigator	岡本宏東北大学, 医学部, 教授 (60025632)
Co-Investigator(Kenkyū-buntansha)	那谷耕司東北大学, 医学部, 助手 (90202233) 高沢伸東北大学, 医学部, 講師 (50187944) 米倉秀人東北大学, 医学部, 助教授 (80240373)
Keywords	cyclic ADP-ribose / second messenger / Ca^<2+>mobilization / pancreatic islet β-cells / insulin secretion / CD38 / ADP-ribosyl cyclase / cyclic ADP-ribose hydrolase
Research Abstract	本研究の目的は、研究代表者らが新しく見出した細胞内情報伝達物質であるサイクリックADPリボースの合成酵素と受容体の構造と性質を明らかにして、サイクリックADPリボースを中心とする新しい細胞内情報伝達系の全容を解明することである。平成6年度の研究は、当初の計画どおりに進行し、以下のような期待された成果を得た。 1.COS-7細胞で発現させたヒト白血球表面抗原CD38を用いた解析より、CD38蛋白はcADPR合成酵素活性(ADP-ribosyl cyclase)とともにcADPR分解活性(cADPR hydrolase)をも有することが新たな知見として得られた。 2.CD38蛋白のcADPR分解活性(cADPR hydrolase)は、膵β細胞でグルコース刺激によって上昇する濃度のATP(2〜10mM)により阻害され、その結果、cADPRの産生量が増加することが明らかとなり、グルコース刺激時の膵β細胞でのcADPR産生の調節機構が解明された。 3.アメフラシ(Aplysia Kurodai)より精製したサイクリックADPリボース合成酵素(ADP-ribosyl cyclase)を用いて〔^<32>P〕標識-8-アジド-サイクリックADPリボースを合成し、サイクリックADPリボースの結合タンパク質/受容体への結合条件を明らかにするとともに、サイクリックADPリボースの結合を指標にして膵β細胞由来の発現cDNAライブラリーのスクリーニングを行い陽性クローンを得た。

Research Products
(43 results)

All Other

All Publications (43 results)

[Publications] Watanabe,T.: "Pancreatic beta-cell replication and amelioration of surgical diabetes by Reg protein." Proceedings of the National Academy of Sciences of the USA. 91. 3589-3592 (1994)
[Publications] Kato,I.: "Transgenic mice overexpressing human vasoactive intestinal peptide gene in pancreatic β-cells." Joural of Biological Chemistry. 269. 21223-21228 (1994)
[Publications] Tohgo,A.: "Essential cysteine residues for cyclic ADP-ribose synthesis and hydrolysis by CD38." Journal of Biological Chemistry. 269. 28555-28557 (1994)
[Publications] Hua,S.H.: "Cyclic ADP-ribose modulates Ca^<2+> release channels for activation by physiological Ca^<2+> entry in bullfrog sympathetic neurons." Neuron. 12. 1073-1079 (1994)
[Publications] Morizumi,S.: "Isoltion,structural determination and expression of a novel reg gene,human regIβ." Biochimica et Biophysica Acta. 1217. 199-202 (1994)
[Publications] Koguma,t.: "Cloning and characterization of cDNA encoding rat ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase (homologue to human CD38)from islets of Langerhans." Biochimica et Biophysica Acta. 1223. 160-162 (1994)
[Publications] Miyashita,H.: "Characterization of the 5'-regulatory region of rat Reg I gene." Biochimica et Biophysica Acta. 1219. 241-243 (1994)
[Publications] Suzuki,Y.: "Structure and expression of a novel rat Reg III gene." Gene. 144. 315-316 (1994)
[Publications] Tohgo,A.: "Structural determination and characterization of a 40kDa protein isolated from rat 40S ribosomal subunit." FEBS Letters. 340. 133-138 (1994)
[Publications] Hirata Y.: "ADP-ribosyl cyclase activity of a novel bone marrow stromal cell surface molecule,BST-1." FEBS Letters. 356. 244-248 (1994)
[Publications] Nagai,A: "Effect of nicotinamide and niacin on bleomycin-induced acute injury and subsequent fibrosis in hamster lungs." Experimental Lung Research. 20. 263-281 (1994)
[Publications] Nakagawara,K.: "Assignment of the gene for human leukocyte antigen CD38,that has cyclic ADP-ribose-synthesizing and-hydrolyzing activities,to chromosome 4p15." Cytogenetics and Cell Genetics. 69. 38-39 (1995)
[Publications] Okamoto,H: "New aspects to the physiological significance of NAD,poly ADP-ribose and cyclic ADP-ribose." Biochimie(special Issue). (in press). (1995)
[Publications] Nata,K.: "The gene structure of the Aplysia Kurodai ADP-ribosyl cyclase,a second-messenger enzyme" Gene. (in press). (1995)
[Publications] Higashida,H.: "Nicotinamide adenine dinucleotide regulates muscarinic receptor-coupled K+(M) channels in rodent NG108-15 cells." Journal of Physiology. (in pres). (1995)
[Publications] Sasaki,T.: "Cyclic ADP-ribose,a novel Ca^<2+>-mobilizing second messenger,operates in airway gland acinar cells." Journal of Clinical Investigation. (in pres). (1995)
[Publications] Okamoto,H.: "New aspects to physiological significance of NAD,poly ADP-ribose and cyclic ADP-ribose." The 11th International Symposium on ADP-ribosylation:DNA Repair,Signal Transduction,Abstracts. 51- (1994)
[Publications] Okamoto,H.: "Perspective on diabetes mellitus-NAD,poly ADP-ribose,cyclic ADP-ribose and REG gene." Journal of the International Society of Pediatrics and Adolescent Diabetess. 30(2). A1- (1994)
[Publications] Okamoto,H.: "A role of cyclic ADP-ribose in stimulus-secretion coupling in pancreatic beta-cells." 15th International Diabetes Federation Congress Abstracts. 15- (1994)
[Publications] Akabane,A.: "Inhibition by nicotinamide of cytokine-induced nitric oxide synthase expression in pancreatic islets." 15th International Diabetes Federation Congress Abstracts. 97- (1994)
[Publications] Yonekura,H.: "Pancreatic beta-cell replication and amelioration of surgical diabetes by Reg protein." 15th International Diabetes Federation Congress Abstracts. 229- (1994)
[Publications] Unno,M.: "Structure and chromosomal location of hyman REG family." 15th International Diabetes Federation Congress Abstracts. 230- (1994)
[Publications] Kato,I.: "Enhanced insulin secretion and improved glucose tolerance in transgenic mice overexpressing human VIP/PHM-27 gene in pancreatic β cells." 15th International Diabetes Federation Congress Abstracts. 313- (1994)
[Publications] 高沢伸: "膵β細胞機能発現の新しい細胞内情報伝達物質 cyclic ADP-ribose." 糖尿病記録号1993. 247-251 (1994)
[Publications] 加藤一郎: "膵ランゲルハンス島β細胞でVIP遺伝子を過剰発現するトランスジェニックマウスの作製と導入遺伝子による血糖降下作用." 分子糖尿病学. 5. 73-80 (1994)
[Publications] 東郷暁: "膵β細胞のセカンドメッセンジャーcyclicADP-riboseの合成系とその調節機構." 糖尿病,Supplement. 37. 224- (1994)
[Publications] 加藤一郎: "ヒトVIP遺伝子導入トランスジェニックマウスにおける血糖降下と耐糖能改善" 糖尿病,Supplement. 37. 225- (1994)
[Publications] 海野倫明: "reg蛋白を膵β細胞で過剰発現するトランスジェニックマウスの作製." 糖尿病,Supplement. 37. 226- (1994)
[Publications] 成島陽一: "マウスRegFamilyの遺伝子構造と染色体座位." 生化学. 66. 1449- (1994)
[Publications] 杉本孝子: "cyclic ADP-ribose 合成酵素遺伝子の構造と発現." 生化学. 66. 1449- (1994)
[Publications] 赤羽敦也: "サイトカイン刺激による膵ランゲルハンス島でのNitric Oxide Synthaseの発現誘導はニコチン酸アミドにより抑制される." 生化学. 66. 657- (1994)
[Publications] 海野倫明: "RegI遺伝子過剰発現トランスジェニックマウスの膵β細胞増殖能." 生化学. 66. 657- (1994)
[Publications] 東郷暁: "CyclicADP-ribose合成酵素の構造、機能とその発現." 生化学. 66. 835- (1994)
[Publications] 篁俊成: "ヒトcyclicADP-ribose合成・分解酵素(CD38)遺伝子の構造と発現." 生化学. 66. 835- (1994)
[Publications] 加藤一郎: "cyclicADP-ribose合成・分解酵素(CD38)遺伝子を膵ランゲルハンス島β細胞で過剰発現するトランスジェニックマウスの作製とその解析." 生化学. 66. 835- (1994)
[Publications] 成島陽一: "4つの遺伝子から構成されるマウスRegファミリーの構造と染色体座位" 生化学. 66. 1066- (1994)
[Publications] Haruhiro Higashida: "NADﾞand cADPR as endogenous regulators of muscarinic receptor-coupled potasseium M channels." 15th International Society for Neurochemistry Biennial Meeting Abstracts. (in press). (1995)
[Publications] Haruhiro Higashida: "NADﾞand cADPR as endogenous regulators of muscarinic receptor coupled potasseium M channels." 4th International Brain Research Organization World Congress Abstracts. (in press). (1995)
[Publications] 小沢輝高: "ラット耳下腺単離小胞体標本によるリアノジン感受性Ca^<++>放出機構" 日本生理学会抄録. (in press). (1995)
[Publications] Yonekura,H.: "Structue and expression of reg gene family.in Frontiers of Insulin Secretion and Pancreatic B-Cell Research" Flatt,P.R.,and Lenzan S.,eds(Smith-Gordon Co.Ltd.)(in press), (1995)
[Publications] Takasawa,S.: "A cyclic ADP-ribose,aNAD^+metabolite,in stimulus-secretion coupling in pancreatic B-cells.in Frontiers of Insulin Secretion and Pancreatic B-Cell Research" Flatt,P.R.,and Lenzan S.eds (Smith Gordon Co.Ltd.)(in press), (1995)
[Publications] Okamoto,H.: "New aspects to the functioning and regeneration of pancreatic β-cells:Cyclic ADP-ribose and Reg gene.in Islet Physiology and Pathophysiology" Soria,B.,ed.(Plenum Press)(in press), (1995)
[Publications] Okamoto,H.: "A role of cyclic ADP-ribose in stimulus-secretion coupling in pancreatic β-cells.B-cells.in Diabetes 1994" Baba,S.,ed(Elsevier), (1995)

1994 Fiscal Year Annual Research Report

新しい細胞内情報伝達物質サイクリックADP-リボースの合成酵素と受容体の解明

Principal Investigator

岡本 宏 東北大学, 医学部, 教授 (60025632)

Research Products

[Publications] Watanabe,T.: "Pancreatic beta-cell replication and amelioration of surgical diabetes by Reg protein." Proceedings of the National Academy of Sciences of the USA. 91. 3589-3592 (1994)

[Publications] Kato,I.: "Transgenic mice overexpressing human vasoactive intestinal peptide gene in pancreatic β-cells." Joural of Biological Chemistry. 269. 21223-21228 (1994)

[Publications] Tohgo,A.: "Essential cysteine residues for cyclic ADP-ribose synthesis and hydrolysis by CD38." Journal of Biological Chemistry. 269. 28555-28557 (1994)

[Publications] Hua,S.H.: "Cyclic ADP-ribose modulates Ca^<2+> release channels for activation by physiological Ca^<2+> entry in bullfrog sympathetic neurons." Neuron. 12. 1073-1079 (1994)

[Publications] Morizumi,S.: "Isoltion,structural determination and expression of a novel reg gene,human regIβ." Biochimica et Biophysica Acta. 1217. 199-202 (1994)

[Publications] Koguma,t.: "Cloning and characterization of cDNA encoding rat ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase (homologue to human CD38)from islets of Langerhans." Biochimica et Biophysica Acta. 1223. 160-162 (1994)

[Publications] Miyashita,H.: "Characterization of the 5'-regulatory region of rat Reg I gene." Biochimica et Biophysica Acta. 1219. 241-243 (1994)

[Publications] Suzuki,Y.: "Structure and expression of a novel rat Reg III gene." Gene. 144. 315-316 (1994)

[Publications] Tohgo,A.: "Structural determination and characterization of a 40kDa protein isolated from rat 40S ribosomal subunit." FEBS Letters. 340. 133-138 (1994)

[Publications] Hirata Y.: "ADP-ribosyl cyclase activity of a novel bone marrow stromal cell surface molecule,BST-1." FEBS Letters. 356. 244-248 (1994)

[Publications] Nagai,A: "Effect of nicotinamide and niacin on bleomycin-induced acute injury and subsequent fibrosis in hamster lungs." Experimental Lung Research. 20. 263-281 (1994)

[Publications] Nakagawara,K.: "Assignment of the gene for human leukocyte antigen CD38,that has cyclic ADP-ribose-synthesizing and-hydrolyzing activities,to chromosome 4p15." Cytogenetics and Cell Genetics. 69. 38-39 (1995)

[Publications] Okamoto,H: "New aspects to the physiological significance of NAD,poly ADP-ribose and cyclic ADP-ribose." Biochimie(special Issue). (in press). (1995)

[Publications] Nata,K.: "The gene structure of the Aplysia Kurodai ADP-ribosyl cyclase,a second-messenger enzyme" Gene. (in press). (1995)

[Publications] Higashida,H.: "Nicotinamide adenine dinucleotide regulates muscarinic receptor-coupled K+(M) channels in rodent NG108-15 cells." Journal of Physiology. (in pres). (1995)

[Publications] Sasaki,T.: "Cyclic ADP-ribose,a novel Ca^<2+>-mobilizing second messenger,operates in airway gland acinar cells." Journal of Clinical Investigation. (in pres). (1995)

[Publications] Okamoto,H.: "New aspects to physiological significance of NAD,poly ADP-ribose and cyclic ADP-ribose." The 11th International Symposium on ADP-ribosylation:DNA Repair,Signal Transduction,Abstracts. 51- (1994)

[Publications] Okamoto,H.: "Perspective on diabetes mellitus-NAD,poly ADP-ribose,cyclic ADP-ribose and REG gene." Journal of the International Society of Pediatrics and Adolescent Diabetess. 30(2). A1- (1994)

[Publications] Okamoto,H.: "A role of cyclic ADP-ribose in stimulus-secretion coupling in pancreatic beta-cells." 15th International Diabetes Federation Congress Abstracts. 15- (1994)

[Publications] Akabane,A.: "Inhibition by nicotinamide of cytokine-induced nitric oxide synthase expression in pancreatic islets." 15th International Diabetes Federation Congress Abstracts. 97- (1994)

[Publications] Yonekura,H.: "Pancreatic beta-cell replication and amelioration of surgical diabetes by Reg protein." 15th International Diabetes Federation Congress Abstracts. 229- (1994)

[Publications] Unno,M.: "Structure and chromosomal location of hyman REG family." 15th International Diabetes Federation Congress Abstracts. 230- (1994)

[Publications] Kato,I.: "Enhanced insulin secretion and improved glucose tolerance in transgenic mice overexpressing human VIP/PHM-27 gene in pancreatic β cells." 15th International Diabetes Federation Congress Abstracts. 313- (1994)

[Publications] 高沢 伸: "膵β細胞機能発現の新しい細胞内情報伝達物質 cyclic ADP-ribose." 糖尿病記録号1993. 247-251 (1994)

[Publications] 加藤一郎: "膵ランゲルハンス島β細胞でVIP遺伝子を過剰発現するトランスジェニックマウスの作製と導入遺伝子による血糖降下作用." 分子糖尿病学. 5. 73-80 (1994)

[Publications] 東郷 暁: "膵β細胞のセカンドメッセンジャーcyclicADP-riboseの合成系とその調節機構." 糖尿病,Supplement. 37. 224- (1994)

[Publications] 加藤一郎: "ヒトVIP遺伝子導入トランスジェニックマウスにおける血糖降下と耐糖能改善" 糖尿病,Supplement. 37. 225- (1994)

[Publications] 海野倫明: "reg蛋白を膵β細胞で過剰発現するトランスジェニックマウスの作製." 糖尿病,Supplement. 37. 226- (1994)

[Publications] 成島陽一: "マウスRegFamilyの遺伝子構造と染色体座位." 生化学. 66. 1449- (1994)

[Publications] 杉本孝子: "cyclic ADP-ribose 合成酵素遺伝子の構造と発現." 生化学. 66. 1449- (1994)

[Publications] 赤羽敦也: "サイトカイン刺激による膵ランゲルハンス島でのNitric Oxide Synthaseの発現誘導はニコチン酸アミドにより抑制される." 生化学. 66. 657- (1994)

[Publications] 海野倫明: "RegI遺伝子過剰発現トランスジェニックマウスの膵β細胞増殖能." 生化学. 66. 657- (1994)

[Publications] 東郷 暁: "CyclicADP-ribose合成酵素の構造、機能とその発現." 生化学. 66. 835- (1994)

[Publications] 篁俊成: "ヒトcyclicADP-ribose合成・分解酵素(CD38)遺伝子の構造と発現." 生化学. 66. 835- (1994)

[Publications] 加藤一郎: "cyclicADP-ribose合成・分解酵素(CD38)遺伝子を膵ランゲルハンス島β細胞で過剰発現するトランスジェニックマウスの作製とその解析." 生化学. 66. 835- (1994)

[Publications] 成島陽一: "4つの遺伝子から構成されるマウスRegファミリーの構造と染色体座位" 生化学. 66. 1066- (1994)

[Publications] Haruhiro Higashida: "NADﾞand cADPR as endogenous regulators of muscarinic receptor-coupled potasseium M channels." 15th International Society for Neurochemistry Biennial Meeting Abstracts. (in press). (1995)

[Publications] Haruhiro Higashida: "NADﾞand cADPR as endogenous regulators of muscarinic receptor coupled potasseium M channels." 4th International Brain Research Organization World Congress Abstracts. (in press). (1995)

[Publications] 小沢輝高: "ラット耳下腺単離小胞体標本によるリアノジン感受性Ca^<++>放出機構" 日本生理学会抄録. (in press). (1995)

[Publications] Yonekura,H.: "Structue and expression of reg gene family.in Frontiers of Insulin Secretion and Pancreatic B-Cell Research" Flatt,P.R.,and Lenzan S.,eds(Smith-Gordon Co.Ltd.)(in press), (1995)

[Publications] Takasawa,S.: "A cyclic ADP-ribose,aNAD^+metabolite,in stimulus-secretion coupling in pancreatic B-cells.in Frontiers of Insulin Secretion and Pancreatic B-Cell Research" Flatt,P.R.,and Lenzan S.eds (Smith Gordon Co.Ltd.)(in press), (1995)

[Publications] Okamoto,H.: "New aspects to the functioning and regeneration of pancreatic β-cells:Cyclic ADP-ribose and Reg gene.in Islet Physiology and Pathophysiology" Soria,B.,ed.(Plenum Press)(in press), (1995)

[Publications] Okamoto,H.: "A role of cyclic ADP-ribose in stimulus-secretion coupling in pancreatic β-cells.B-cells.in Diabetes 1994" Baba,S.,ed(Elsevier), (1995)

岡本宏東北大学, 医学部, 教授 (60025632)

[Publications] 高沢伸: "膵β細胞機能発現の新しい細胞内情報伝達物質 cyclic ADP-ribose." 糖尿病記録号1993. 247-251 (1994)

[Publications] 東郷暁: "膵β細胞のセカンドメッセンジャーcyclicADP-riboseの合成系とその調節機構." 糖尿病,Supplement. 37. 224- (1994)

[Publications] 東郷暁: "CyclicADP-ribose合成酵素の構造、機能とその発現." 生化学. 66. 835- (1994)