1998 Fiscal Year Final Research Report Summary
ADP-RIBOSYLTRANSFERASE OF HELIOBACTER PYLORI
| Project/Area Number |
09044322
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Nagasaki University |
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Principal Investigator |
HIRAYAMA Toshiya NAGASAKI UNIVERSITY, INSTITUTE OF TOROPICAL MEDICEINE, PROFESSOR, 熱帯医学研究所, 教授 (50050696)
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| Co-Investigator(Kenkyū-buntansha) |
MOSS Joel NATIONAL INSTITUTES OF HEALTH,NATIONAL HEART, LUNG, AND BLOOD INSTITUTE, CHIEF, 部長
WADA Akihiro NAGASAKI UNIVERSITY, INSTITUTE OF TOROPICAL MEDICEINE, RESEARCH ASSOCIATE, 熱帯医学研究所, 助手 (70253698)
NODA Masatoshi CHIBA UNIVERSITY SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (60164703)
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| Project Period (FY) |
1997 – 1998
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| Keywords | HELICOBACTER PYLORI / ADP-RIBOSYLTRANSFERASE / BACTERIAL TOXIN / ETIOLOGIC AGENT / BACTERIAL INFECTION |
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| Research Abstract |
HELICOBACTER PYLORI IS AN ETIOLOGIC AGENT FOR CHRONlC GASTRITIS. DUODENAL ULCERS. AND GASTRIC MUCOUS MALIGNANCY. TO VESTIGATE FACTORS INVOLVED IN THE PATHOGENESIS OF THE MICROORGANISM. WE EXAMlNED WHETHER H. PYLORI PRODUCES AN ADP-RIBOSYLTRANSFERASE (ART) AND WHETHER AN ANTI-ULCER DRUG CAN INHIBIT THE ENZYME ACTIVITY. SONIFIED CULTURE OF THE BACTERIA WAS SUBJECTED TO ART ASSAY IN WHICH THE EXTRACT WAS INCUBATED WITH [ADENYLATE-32P]NAD. WHEN THE ASSAY MIXTURE WAS ANALYZED BY SDS-PAGE AND AUTORADIOGRAPHY, RADIOLABELELLING OF A 70KDA PROTEIN (P70) IN THE CELL LYSATE WAS OBSERVED IN A MG2+-DEPENDENT MANNER. THE MODIFICATION OF P70 SEEMED TO BE MEDIATED BY A MONO-ART, AND INVOLVEMENT OF NON-ENZYMATIC NAD-DEPENDENT MODIFICATIONS APPEARED TO BE UNLIKELY. THE OBSERVATIONS THAT (ADP-RIBOSE)-P70 LINKAGE WAS SUSCEPTIBLE TO HYDROXYLAMlNE TREATMENT AND THAT ARGlNlNE AND AGMATINE INHIBITED THE MODIFICATION OF P70 INDICATED THAT ARGlNlNE RESIDUE IN P70 IS THE SITE OF THE MODIFICATION. ADDITIONALLY, AGMATINE COULD BE UTILIZED AS A SUBSTRATE BY THE PUTATIVE ENZYME IN A MG2+-DEPENDENT MANNER. H. PYLORI ART WAS NOT ACTIVATED BY ARF, A SMALL GTP-BINDlNG PROTEIN WHICH IS STIMULATE ART ACTIVITY OF CHOLERA ENTEROTOXlN. AN ANTI-ULCER COMPOUND, REBAMIPIDE, INHIBITED THE ADP-RIBOSYLATION BOTH OF P70 AND OF AGMATINE BY H. PYLORI CELL LYSATE. SUGGESTlNG THAT THE ENZYME CAN BE A TARGET OF THE DRUG. THESE RESULTS INDICATE THAT H. PYLORI PRODUCES A CELL-ASSOCIATED ARGlNlNE-SPECIFIC MONO-ART, WHICH IS SUSCEPTIBLE TO ANTI-ULCER DRUG. FURTHERMORE. INCUBATION OF H. PYLORI LYSATE WITH THE MOMOGENATE OF HL-60 CELLS CAUSED THE MODIFICATION OF A 50KDA PROTElN, SUGGESTING THAT THE ENZYME MAY ALSO ADP-RIBOSYLATE HOST CELL PROTEIN. BECAUSE MANY BACTERIAL PATHOGEN PRODUCE TOXINS WITH MONO-ART ACTIVITY, THE RESULTS MAY SUGGEST THAT H. PYLORI ART PLAYS A ROLE IN PATHOLOGICAL EFFECT OF THE BACTERlUM.
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[Publications] YAHIRO,Kinnosuke, NIIDOME,Takuro, KIMURA,Miyuki, HATAKEYAMA,Tomomitsu, AOYAGI,Haruhiko, KURAZONO,Hisao, IMAGAWA,Ken-ichi, WADA,Akihiro, JOEL MOSS, AND HIRAYAMA,Toshiya: "Activation of Helicobacter pylori VacA toxin by alkaline or acid conditions increases its binding to a 250-kDa-protein, receptor protein tyrosine phosphatase (RPTP) β"J. Biol. Chem.. (in press). (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] NAGATA,Hiroshi, WADA,Akihiro, KURAZONO,Hisao, YAHIRO,Kinnosuke, SHIRASAKA,Daisuke, IKEMURA,Takahiro, AOYAMA,Nobuo, Wang Ai Ping, MAKIYAMA,Kazuya, KOHNO,Shigeru, and HIRAYAMA,Toshiya: "Application of bead-ELISA method to detect Helicobacter Pylori VacA"Microb. Pathog.. (in press). (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] KIMURA,Miyuki, GOTO,Shinji, WADA,Akihiro, YAHIRO,Kinosuke, NIIDOME,Takuro, HATAKEYAMA,Tomomitsu, AOYAGI,Haruhiko, HIRAYAMA,Toshiya, and KONDO,Takahito: "Vacuolating cytotoxin purified from Helicobacter pylori causes mitochondorial damage in human gastric cells"Microb. Pathog.. 26. 45-52 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] YASHIRO,Kinnosuke, NIIDOME,Takuro, HATAKEYAMA,Tomomitsu, AOYAGI,Haruhiko, KURAZONO,Hisao, Philip Ian Padilla, WADA,Akihiro, HIRAYAMA,Toshiya: "Helicobacter pylori vacuolating cytotoxin (VacA) binds to the 140kDa protein in human gastric cancer cell lines, AZ-521 and AGS"Biochem. Biophys. Res. Commun. 238. 629-632 (1997)
Description
「研究成果報告書概要(欧文)」より
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