• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

THE CLINICAL FEATURES AND PATHOGENESIS IN MITOCHONDRIAL DNA MUTATION : BASIC STUDY FOR GENE THERAPY

Research Project

Project/Area Number 09670487
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionYokohama City University Hospital

Principal Investigator

SATOH Shinobu  University Hospital, Assistant Professor, 医学部・附属病院, 講師 (80244424)

Co-Investigator(Kenkyū-buntansha) SEKIHARA Hisahiko  School of Medicine, Professor, 医学部, 教授 (80126094)
ONISHI Hideki  School of Medicine, Assistant Professor, 医学部, 講師 (30275028)
SAITO Tatsuya  School of Medicine, Associate Professor, 医学部, 助教授 (90205659)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsmitochondrial disease / pancreatic exocrine / spontaneous abortion / ileus / mitochondrial DNA / ethidiumbromide / differentiation / gucose transport / 筋細胞分化 / インスリン作用不全 / 発育障害 / 消化管機能異常 / 遺伝子治療 / ミトコンドリアDNA異常
Research Abstract

Mitochondrial DNA (mtDNA) mutations are associated with various disease. Recent studies have shown that there is a close association between the nt 3243 of t RNA^<Leu(UUR)> gene (A3243G mutation) and maternally inherited diabetes mellitus (DM). Multiorgan involvement has been suggested. As a test of exocrine pancreatic function, we performed a bentiromide test using benzoyl-tyrosyl-p-aminobenzoic acid (PABA). % recovery of PABA decreased at a range 19-68% (cf normal 81.9 8.5% ; DM 77.0 12.6%). The percentage of mutant mtDNA ranged from 6-63%. This result indicated that exocrine pancreatic dysfunction may be associated with the A3243G mutation. We have calculated the prevalence of spontaneous abortion in 379 women who delivered children in our hospital. The prevalence of spontaneous abortion was 14.4% (spontaneous abortion/total pregnancy=96/717). In our study, the prevalence of spontaneous abortion was higher in the population with the mutation than that of general population (25.0 vs 13.4%). In the basic study, we used C_2C_<12> myoblast treated with ethidium bromide 250 ng/ml for 10 days in medium. The cell line C2C12 was treated with EB for 10 days, and total RNA extract from cells from the cells. After 10 days incubation with EB, no mtRNA was detectable in C_2C_<12> cells, but the contents of beta-actin were not affected. After 60% confluent, we changed medium to 2% horse serum, 50 mug/ml uridine and 0.1 mg/ml pyruvate. Differentiation to myotubes in C_2C_<12> cells with EB was remarkably impaired. We also study the effect of EB in differentiated C_2C_<12> myotubes on insulin stimulated glucose transport. C_2C_<12> myotubes were treated with EB 3 days, and 2-deoxyglucose transport was measured. Insulin-stimulated glucose transport activity was decreased in C_2C_<12> myotubes treated with EB.In conclusion, we observed variable clinical symptoms in the patients and lacking of mtDNA induced a impaired muscle differentiation and its function in culture cells.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Onishi H, et al: "Depressive disorder due to mitochondrial transfer RNA^<Leu(UUR)> mutation" Biol Psychiatry. 41. 1137-1139 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kaburagi Y, Satoh S et al: "Role of insulin receptor substrale-1 and pp60 in the Regulation of insulin-induced glucose transport and GLUT4 translocation in primary adipocytes" J.Biol.Chem. 272. 25839-25844 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshikawa T, Satoh, et al: "Insulin resistance and the alternations of GLUT4 in adipose cells from cachectic tumor-bearing rats" J Parenteral and Enteral Nutrition. 21. 347-349 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Onishi H, Satoh S, et al: "Pancreatic exocrine dysfunction associated with mitochondrial t RNA^<Leu(UUR)> mutation" J.Medical Genetics. 35. 255-257 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shimizu Y, Satoh S et al: "Effects of noradrenaline on the cell surface glucose transporters in cultured brown adipocytes" Biochem.J. 330. 397-403 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Arai T, Satoh et al: "Ocular arterial flow hemodynamics in patients with diabetes mellitus" J Ultrasound. 17. 675-691 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ito T, Satoh S, et al: "Expression of facilitative glacosc transporters isoforms in lung carcinomas" Modern Pathol. 11. 437-443 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mukasa K et al: "Dehydroepiandrosterone (DHEA) ameliorates the insulin sensitivity in older rats" J Steroid Biochem Molecular Biology. 67. 355-358 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Terauchi Y, Satoh S et al: "Increased insulin sensitivity and hypoglycemia in mice lacking the p850 subunit of phosphoinositide 3-kinase" Nature Genetics. 21. 230-235 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshikawa T, Satoh S et al: "Inhibition of insulin-stimulated phosphorylation and the alterations of GLUT4 in an isolated adipose cells from tumor bearing rats" Biochem Biophys Res Comm. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Noguchi Y, Satoh S et al: "Glucose uptake in the human gastric cancer cell line, MKN28, is increased by insulin stimulation" Cancer Letter. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Noguchi Y, et al: "Expression of facilitative glucose transporters in gastric tumor" Hepatogastroenterology. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ysushi Kaburagi, Shinobu Satoh, et al: "Role of insulin receptor substrate-1 and pp60 in the regulation of insulin-induced glucose transport and GLUT4 translocation in primary adipocytes." J Biological Chemistry. 272. 25839-25844 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideki Onishi et al: "Depressive disorder due to mitochondrial transfer RNA^<Leu (UUR)> mutation." Biol Psychiatry. 41. 1137-1139 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takaki Yoshikawa, Yoshikazu Noguchi, Shinobu Satoh, et al: "Insulin resistance and the alternations of GLUT4 in adipose cells from cachectic tumor-bearing rats." J.Parenteral and Enteral Nutrition. 21. 347-349 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideki Onishi, et al, Shinobu Satoh: "Pancreatic exocrine dysfunction associated with mitochondrial tRNA^<Leu (UUR)> mutation." J.Medical Genetics. 35. 255-257 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasutake Shimizu, Shinobu Satoh, et al: "Effects of noradrenaline on the cell surface glucose transporters in cultured brown adipocytes : Novel mechanism for selective activation of GLUT1 glucose transporters." Biochem.J.330. 397-403 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takasi Arai, et al: "Ocular arterial flow hemodynamics in patients with diabetes mellitus." J Ultrasound. 17. 675-691 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takaaki Ito, Shinobu Satoh et al: "Expression of facilitative glucose transporters isoforms in lung carcinomas : Its relation to histologic type, differentiation grade, and tumor stage." Modern Pathology. 11. 437-443 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koji Mukasa, et al: "Dehydroepiandosterone (DHEA) ameliorates the insulin sensitivity in older rats." J Steroid Biochem Molecular Biology. 67. 355-358 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasuo Terauchi, Yuuki Tsuji, Shinobu Satoh: "Increased insulin sensitivity and hypoglycemia in mice lacking the p85alpha Subunit of phosphoinositide 3-kinase." Nature Genetics. 21. 230-235 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshikawa T, Satoh S, et al: "Inhibition of insulin-stimulated phosphorylation and the alterations of GLUT4 in an isolated adipose cells from tumar-bearing rats -possible mechanism of insulin resistance in cancer cachexia-" Biochem Biophys Res Comm. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshikazu Noguhi, Shinobu Satoh, et al: "Glucose uptake in the human gastric cancer cell line, MKN28, is increased by insulin stimulation" Cancer Letter. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshikazu Noguchi, et al: "Expression of facilitative glucose transporters in gastric tumors." Hepatpgastroenterolory. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Noguchi Y et al: "Insulin resistance in cancer patients is associated with enhanced tumor necrosis factor-alpha expression in skellal muscle" Biochem Biophys Res comm. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Terauch Y,Tsuji Y,Satoh S.et al: "Increased insulin sensilivity and hypoglycemia in mice lacking the p85f subunit of phosphoinositide 3-kinase" Nature Genetics. 21・2. 230-235 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Onishi H,et al,Satoh S: "Pancreatic exocrine dysfunction associated with mitochondrial tRNAleu(UUR) mutation" J Medical Genetics. 35・3. 255-257 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ito,T.Noguchi Y.Satoh S: "Expression of facelitative glucose transporter in lung carcinoma" Mod Pathol. 11・5. 437-443 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mukasa K.et al: "Dehydroepiandrosterone(DHEA)ameliorates the insulin sensitivity in older rats" J Steroid Biochem Molec Biol. 67・4. 355-358 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Arai T.et al: "Ocular arterial flow hemcdynamics in patient with diabetes mellitus" J Ultrasound Med. 17. 675-681 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Onishi H, et al Satoh S: "Pancreatic exocrine dysfunction associated with mitochondrial ^t RNA^<leu(UUR)> nutation" J Medical Genetics. (印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshikawa T et al: "Insulin resistance and the alteration of GLUT4 in adipose cells from cachectic tumor-bearing rats" J Parenteral Enteral Nutrition. (印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] Shimizu Y, Satoh S et al: "Effects of noradrenaline on the surface glucose transporters in culture rat brown adipocytes" Biochemical J. 330. 397-403 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kaburagi Y, Satoh S et al: "Role of insulin receptor substrate-1 and pp60 in the regulation of insulin induced guicose transport and GLUT4 translocation in primary adipocyles" J Biological Chemistry. 272. 25839-25844 (1997)

    • Related Report
      1997 Annual Research Report

URL: 

Published: 1997-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi