1994 年度実績報告書

新しい細胞内情報伝達物質cyclicADP-riboseの定量法の開発

研究課題

研究課題/領域番号	05558084
研究機関	東北大学
研究代表者	米倉秀人東北大学, 医学部, 助教授 (80240373)
研究分担者	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) 岡本宏東北大学, 医学部, 教授 (60025632)
キーワード	cyclicADP-ribose / second messenger / Cs^<2+>mobilization / pancreatic islet β-cells / insulin secretion / 定量法 / 抗cyclicADP-ribose抗体
研究概要	本研究の目的は、最近研究代表者らが膵ランゲルハンス島β細胞のインスリン分泌過程において見いだした新しい細胞内情報伝達物質であるcyclicADP-riboseの定量法を開発・確立することである。cyclicADP-riboseは、cyclicADP-ribose合成酵素(ADP-ribosyl cyclase)によりNADから合成され、小胞体からカルシウムイオンを動員して、細胞内カルシウムイオン濃度を上昇させるカセンドメッセンジャーとして機能している。平成6年度の研究は、以下のとうりに進行し、期待された成果が得られた。 1.平成5年度に調整した2′-O-サクシニルcyclicADP-riboseをチロシンメチルエステル化した後、クロラミンT法または酵素法で^<125>I標識し^<125>I-2′-O-サクシニルcyclicADP-riboseを調製した。 2.^3H-,^<14>C-,^<32>P-標識NADからcyclicADP-ribose合成酵素を用いて標識cyclicADP-riboseを調製し、この標識cyclicADP-riboseをサクシニル化し、^3H-,^<14>C-,^<32>P-2′-O-サクシニルcyclicADP-riboseを調製した。 3.平成5年度に調製した抗cyclicADP-ribose血清と1.,2.で調製した放射標識cyclicADP-riboseを用いた競合法で、種々のcyclicADP-riboseの構造類似体と標準cyclicADP-riboseを様々な割合で混合したものを用いてcyclicADP-ribose測定の特異性の検討を行なっている。

研究成果

(43件)

すべてその他

すべて文献書誌 (43件)

[文献書誌] 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)
[文献書誌] Kato,I.: "Transgenic mice overexpressing human vasoacitive intestinal peptide gene in pancreatic β-cells." Journal of Biological Chemistry. 269. 21223-21228 (1994)
[文献書誌] Tohgo,A.: "Essential cysteine residues for cyclic ADP-ribose synthesis and hydrolysis by CD38." Journal of Biological Chemistry. 269. 28555-28557 (1994)
[文献書誌] 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)
[文献書誌] Moriizumi,S.: "Isolation,Structural determination and expression of a novel reg gene,human regIβ。" Biochimica et Biophysica Acta. 1217. 199-202 (1994)
[文献書誌] 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)
[文献書誌] Miyashita,H.: "Characterization of the 5′-regulatory region of rat Reg I gene." Biochimica et Biophysica Acta. 1219. 241-243 (1994)
[文献書誌] Suzuki,Y.: "Structure and expression of a novel rat Reg III gene." Gene. 144. 315-316 (1994)
[文献書誌] Tohgo,A.: "Structural determination and chaeractrerization of a 40 kDa protein isolated from rat 40S ribosomal subunit." FEBS Lettrs. 340. 133-138 (1994)
[文献書誌] Hirata,Y.: "ADP-ribosyl cyclase activity of a novel bone marrow stromal cell surface molecule,BST-1." FEBS Lettrs. 356. 244-248 (1994)
[文献書誌] 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)
[文献書誌] Nakagawara,K.: "Assignment of the gene for human leukocyte antigen CD38,that has cyclicADP-ribose-synthesizing and -hydrolyzing activities,to chromosome4p15." Cytogenetics and Cell Genetics. 69. 38-39 (1995)
[文献書誌] Okamoto,H: "New aspects to the physiological significance of NAD,poly ADP-ribose and cyclic ADP-ribose." Biochimie(Special Issue). in press. (1995)
[文献書誌] Nata,K.: "The gene structure of the Aplysia kurodai ADP ribosyl cyclase,a second-messenger enzyme" Gene. in press. (1995)
[文献書誌] Hibashida,H.: "Nicotinamide adenine dinucleotide regulates muscarinic receptor-coupled K+(M)channels,inrodent NG108-15cells." Journal of Physiology. in pres. (1995)
[文献書誌] 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)
[文献書誌] Okamoto,H: "New aspects to physiological significance of NAD,poly ADP-ribose and cyclic ADP-ribose." The 11th Intenational Symposium on ADP-ribosylation:DNA Repair Signal Transduction,Abstracts. 51 (1994)
[文献書誌] 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)
[文献書誌] Okamoto,H: "Arole of cyclicADP-ribose in stimulus-secretion coupling in pancreatic beta-cells." 15th International Diabetes Federation Congress Abstracts. 15 (1994)
[文献書誌] Akabane,A.: "Inhibition by nicotinamide of cytokine-induced nitric oxide synthase expression in Pancreatic islets." 15th International Diabetes Federation Congress Abstracts. 97 (1994)
[文献書誌] Yonekura,H.: "Pancreatic beta-cell replication and amelioration of surgical diabetes by Reg protein." 15th International Diabetes Federation Congress Abstracts. 299 (1994)
[文献書誌] Unno,M.: "Structure and dhromosomal location of human REG family." 15th International Diabetes Federation Congress Abstracts. 230 (1994)
[文献書誌] 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)
[文献書誌] 高沢伸: "膵β細胞機能発現の新しい細胞内情報伝達物質cyclicADP-ribose." 糖尿病記録号1993. 247-251 (1994)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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. 275 (1994)
[文献書誌] 海野倫明: "reg蛋白を膵β細胞で過剰発現するスランスジェニックマウスの作製." 糖尿病,Supplement. 37. 226 (1994)
[文献書誌] 成島陽一: "マウスReg Faimilyの遺伝子構造と染色体座位." 生化学. 66. 1449 (1994)
[文献書誌] 杉本孝子: "cyclicADP-ribose合成酵素遺伝子の構造と発現." 生化学. 66. 1449 (1994)
[文献書誌] 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)
[文献書誌] 海野倫明: "RegI遺伝子過剰発現トランスジエニックマウスの膵β細胞増殖能." 生化学. 66. 657 (1994)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Haruhiro Higashida: "NAD^+ and cADPR as endogenous regulators of muscarinic receptor-coupled M channels." 15th International Society for Neurochemistry Biennial Meeting Abstracts. in press. (1995)
[文献書誌] Haruhiro Higashida: "NAD^+ and cADPR as endogenous regulators of muscarinic receptor-coupled M channels." 4th Intenational Brain Research Organization World Congress Abstracts. in press. (1995)
[文献書誌] 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)
[文献書誌] Yonekura,H.: "Stuctue and expression of reg 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)
[文献書誌] Takasawa,S.: "A cyclic ADP-ribose,a NAD+metabolite,in stimulus-secretion coupling in pancreatic B-cells.in Frontiers of Insulin Secretion and Pancreatic B-Cell Researdh" Flatt,P.R.,and Lenzan S,eds(Smith-Gordon Co.Ltd)(in press), (1995)
[文献書誌] Okamoto,H.: "New aspects to the functioning and regeneration of pancreatic β-cells:CyclicADP-ribose and Reg gene.in Islet Physiology and Pathophysiology" Soria,B.,ed.(Plenum Press)(in press), (1995)
[文献書誌] Okamoto,H.: "A role of cyclicADP-ribose in stimulus-secretion coupling in pancreatic β-cslls.B-cells.in Diabetes 1994" Baba,S,ed.(Elsevier)(in press), (1995)

1994 年度 実績報告書

新しい細胞内情報伝達物質cyclicADP-riboseの定量法の開発

研究代表者

米倉 秀人 東北大学, 医学部, 助教授 (80240373)

研究成果

[文献書誌] 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)

[文献書誌] Kato,I.: "Transgenic mice overexpressing human vasoacitive intestinal peptide gene in pancreatic β-cells." Journal of Biological Chemistry. 269. 21223-21228 (1994)

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

[文献書誌] 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)

[文献書誌] Moriizumi,S.: "Isolation,Structural determination and expression of a novel reg gene,human regIβ。" Biochimica et Biophysica Acta. 1217. 199-202 (1994)

[文献書誌] 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)

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

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

[文献書誌] Tohgo,A.: "Structural determination and chaeractrerization of a 40 kDa protein isolated from rat 40S ribosomal subunit." FEBS Lettrs. 340. 133-138 (1994)

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

[文献書誌] 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)

[文献書誌] Nakagawara,K.: "Assignment of the gene for human leukocyte antigen CD38,that has cyclicADP-ribose-synthesizing and -hydrolyzing activities,to chromosome4p15." Cytogenetics and Cell Genetics. 69. 38-39 (1995)

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

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

[文献書誌] Hibashida,H.: "Nicotinamide adenine dinucleotide regulates muscarinic receptor-coupled K+(M)channels,inrodent NG108-15cells." Journal of Physiology. in pres. (1995)

[文献書誌] 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)

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

[文献書誌] 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)

[文献書誌] Okamoto,H: "Arole of cyclicADP-ribose in stimulus-secretion coupling in pancreatic beta-cells." 15th International Diabetes Federation Congress Abstracts. 15 (1994)

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

[文献書誌] Yonekura,H.: "Pancreatic beta-cell replication and amelioration of surgical diabetes by Reg protein." 15th International Diabetes Federation Congress Abstracts. 299 (1994)

[文献書誌] Unno,M.: "Structure and dhromosomal location of human REG family." 15th International Diabetes Federation Congress Abstracts. 230 (1994)

[文献書誌] 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)

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

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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. 275 (1994)

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

[文献書誌] 成島陽一: "マウスReg Faimilyの遺伝子構造と染色体座位." 生化学. 66. 1449 (1994)

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

[文献書誌] 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)

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

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

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

[文献書誌] Haruhiro Higashida: "NAD^+ and cADPR as endogenous regulators of muscarinic receptor-coupled M channels." 4th Intenational Brain Research Organization World Congress Abstracts. in press. (1995)

[文献書誌] 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)

[文献書誌] Yonekura,H.: "Stuctue and expression of reg 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)

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

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

[文献書誌] Okamoto,H.: "A role of cyclicADP-ribose in stimulus-secretion coupling in pancreatic β-cslls.B-cells.in Diabetes 1994" Baba,S,ed.(Elsevier)(in press), (1995)

1994 年度実績報告書

米倉秀人東北大学, 医学部, 助教授 (80240373)

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