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

Structure and function of novel genes which differentially expressed in cardiac hypertrophy of carnitine deficiency

Research Project

Project/Area Number 10470042
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionKagoshima University

Principal Investigator

SAHEKI Takeyori  Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (10056070)

Co-Investigator(Kenkyū-buntansha) IIJIMA Mikio  Kagoshima University, Faculty of Medicine, Research Associate, 医学部, 助手 (00305111)
HORIUCHI Masahisa  Kagoshima University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (50264403)
KOBAYASHI Keiko  Kagoshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (70108869)
安田 いづみ  鹿児島大学, 医学部, 助手 (10305112)
Project Period (FY) 1998 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1998: ¥8,000,000 (Direct Cost: ¥8,000,000)
KeywordsCardiac hypertrophy / Carnitine deficiency / CDV (carnitine deficiency-associated genes) / Juvenile visceral steatosis (JVS) mice / Long-chain fatty acid / Octn2 / PDK4 / カルニチン欠乏 / カルニチン膜輸送体
Research Abstract

Carnitine is an essential co factor for β-oxidation of long-chain fatty acids. Juvenile visceral steatosis (JVS) mice have been reported as an animal model for Reye-like syndrome in 1988, suffering from fatty liver, hypoglycemia, hyperammonemia and growth retardation. Then, the mice have been established as an animal model for systemic carnitine deficiency caused by a defect of plasma membrane carnitine transport protein, Octn2. One of the most notable symptoms of the mice is cardiac hypertrophy. In the present study, we characterized the structure and function of three novel genes which differentially expressed in the ventricles of JVS mice, CDV-1, -2, and -3 (carnitine-deficiency-associated genes expressed in ventricle). CDV-1 is heart-specific gene and specifically suppressed in the hypertrophied ventricles of JVS mice, while CDV-1R is CDV-1 related gene which is expressed not only in the heart but also in the kidney and brain and not differentially expressed. CDV-1 mRNA is constructed from the 3'-half of CDV-1R and the presumed promoter sequence for CDV-1 locates in the intron 14. CDV-2 is highly expressed in the ventricles of JVS mice and was found to be a mouse homolog of pyruvate dehydrogenase kinase 4 (PDK4). The cardiac expression of CDV-3 is also augmented in the ventricles of JVS mice and suppressed by the carnitine treatment. The sequence analysis revealed that CDV-3 has a high similarity to a human predicted nuclear protein (H41) which has been reported to be up-regulated in breast cancer cells overexpressed c-erbB-2 (a kind of tyrosine kinase). These results suggest that CDV-1 and CDV-3 are directly involved in cardiac hypertrophy and CDV-2, or PDK4, is more related to carnitine deficiency. Effect of dietary lipid on the development of cardiac hypertrophy is also reported.

Report

(5 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Horiuchi M, et al.: "Secondary abnormality of carnitine biosynthesis results from carnitine reabsorptional system defect in juvenile visceral steatosis mice"Biochim. Biophys. Acta. 1362. 263-268 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jalil M.A, et al.: "Catecholamine metabolism bitors and receptor blockades only partially suppress cardiac hypertrophy of juvenile visceral steatosis mice with systemic carnitine deficiency"Life Sciences. 64. 1137-1144 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuwajima M, et al.: "Cardiomegaly in the juvenile viscral steatosis (JVS) mouse is reduced with acute elevation of heart short-chain acyl-carnitine level after L-carnitine injection"FEBS Lett.. 443. 261-266 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Horiuchi M, et al.: "Pyruvate dehydrogenase kinase 4 mRNA increases in ventricles under starvation and under carnitine deficiency"Bio Factors. 10. 301-309 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saheki T, et al.: "Pathogenesis of hyperammonemia : Mechanism of hyperammonemia found in carnitine-deficient juvenile visceral steatosis (JVS) mice"Guanidino Compounds in Biology and Medicine. 17-27 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 佐伯 武頼: "ビタミン様作用物質-カルニチン"日本臨床. 57(10). 108-113 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Musa DMAA, et al.: "Involvement of a cis-acting element in the suppression of carbamoyl phosphate synthetase I gene expression in the liver of carnitine-deficient mice"Mol. Genet. Metab.. 68(3). 346-356 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshida G, et al.: "The signaling pathway of cardiotrophin-1 is not activated in hypertrophied ventricles of carnitine-deficient juvenile visceral steatosis (JVS) mice"in vivo. 14. 401-406 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Higashi M, et al.: "Genomic organization and mapping of mouse CDV (carnitine deficiency-associated gene expressed in ventricle)-1 and its related CDV-1R gene"Mammal. Genom.. 11. 1053-1057 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saheki T, et al.: "<Minireview> Antagonizing effect of AP-1 on glucocorticoid induction of urea cycle enzymes : a study of hyperammonemia in carnitine-deficient, juvenile visceral steatosis mice"Mol. Genet. Metab.. 71. 545-551 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Li MX, et al.: "Hyperammonemia in carnitine-deficient JVS mice at adult age caused by starvation"Metab. Brain Dis.. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 佐伯武頼, 小林圭子: "新ミトコンドリア学"共立出版. 6 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Horiuchi M, et al.: "Secondary abnormality of carnitine biosynthesis results from carnitine reabsorptional system defect in juvenile visceral steatosis mice"Biochim, Biophys. Acta. 1362. 263-268 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jalil MA, et al.: "Catecholamine metabolism bitors and receptor blockades only partially suppress cardiac hypertrophy of juvenile visceral steatosis mice with systemic carnitine deficiency"Life Sciences. 64. 1137-1144 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuwajima M, et al.: "Cardiomegaly in the juvenile viscral steatosis (JVS) mouse is reduced with acute elevation of heart short-chain acyl-carnitine level after L-carnitine injection"FEBS Lett.. 443. 261-266 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Horiuchi M, et al.: "Pyruvate dehydrogenase kinase 4 mRNA increases in ventricles under starvation and under carnitine deficiency"Bio Factors. 10. 301-309 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saheki T, et al.: "Pathogenesis of hyperammonemia : Mechanism of hyperammonemia found in carnitine-deficient juvenile visceral steatosis (TVS) mice"Guanidino Compounds in Biology and Medicine. 17-27 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Musa DMAA, et al.: "Involvement of a cis-acting element in the suppression of carbamoyl phosphate synthetase I gene expression in the liver of carnitine-deficient mice"Mol. Genet. Metab.. 63(3). 346-356 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshida G, et al.: "The signaling pathway of cardiotrophin-1 is not activated in hypertrophied ventricles of carnitine-deficient juvenile visceral steatosis (JVS) mice"in vivo. 14. 401-406 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Higashi M, et al.: "Genomic organization and mapping of mouse CDV(carnitine deficiency-associated gene expressed in ventricle)-1and its related CDV-1R gene"Mammal. Genom.. 11. 1053-1057 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saheki T, et al.: "<Minireview> Antagonizing effect of AP-1 on glucocorticoid induction of urea cycle enzymes : a study of hyperammonemia in carnitine-deficient, juvenile visceral steatosis mice"Mol. Genet. Metab.. 71. 545-551 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Li MX, et al.: "Hyperammonemia in carnitine-deficient JVS mice at adult age caused by starvation"(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Li MX, Kobayashi K, et al.: "Hyperammonemia in carnitine-deficient JVS mice at adult age caused by starvation"Metab.Brain Dis.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 佐伯武頼, 小林圭子: "新ミトコンドリア学"共立出版. 6 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Goichiro Yoshida et al.: "The signaling pathway of cardiotrophin-1 is not activated in hypertrophied ventricles of carnitine-deficient juvenile visceral steatosis (JVS) mice"in vivo. 14. 401-406 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mikiko Higashi et al.: "Genomic organization and mapping of mouse CDV (camitine deficiency-associated gene expressed in ventricle)-1 and its related CDV-1R gene"Mammalian Genome. 11. 1053-1057 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeyori Saheki et al.: "<Minireview> Antagonizing effect of AP-1 on glucocorticoid induction of urea cycle enzymes : a study of hyperammonemia in carnitine-deficient, juvenile visceral steatosis mice"Mol Genet Metabol. 71. 545-551 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masahisa Horiuchi et al.: "Secondary abnormality of carnitine biosynthesis results from carnitine reabsorptional system defect in juvennile visceral steatosis mice."Biochim.Biophys.Acta. 1362. 263-268 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Md.Abdull jalil et al.: "Catecholamine metabolism inhibitors and receptor blockades only partially suppress cardiac hypertrophy of juvenile visceral steatosis mice with systemic carnitine deficiency"Life Sciences. 64. 1137-1144 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masamichi Kuwajima et al.: "Cardiomegaly in the juvenile visceral steatosis(JVS) mouse is reduced with acute elevation of heart short-chain acyl-carnitine level after L-carnitine injection."FEBS Lett.. 443. 261-266 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masahisa Horiuchi et al.: "Pyruvate dehydrogenase kinase 4 mRNA increases in ventricles under starvation and under carnitine deficiency."Bio Factors. 10. 301-309 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 佐伯武頼: "ビタミン様作用物質-カルニチン"日本臨床. 57(10). 108-113 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Dewan Md.Abdullah Abu Musa et al.: "Involvement of a cis-Acting Element in the Suppression of Carbamoyl Phosphate Synthtase I Gene Expression in the Liver of Carnitine-Deficient Mice"Molecular Genetics and Metabolism. 68(3). 346-356 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Saheki T: "Pathogenesis of hyperammonemia-Mechanism of hyperammonemia found in carnitine-deficient juvenile visceral steatosis(JVS)mice-." Guanidino Compounds in Biology and Medicine. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Horiuchi M: "Pyruvate dehydrgenase kinase 4 mRNA increases in ventricles under starvation and under carnitine deficiency." Bio Factors. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kuwajima M: "Cardiomegaly in the juvenile visceral steatosis(JVS)mouse is reduced with acute elevation of heart short-chain acyl-carnitine level after L-carnitine injection." FEBS Lett.443. 261-266 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Jalil MA: "Catecholamine metabolism inhibitors and receptor blockades only partially suppress cardiac hypertrophy of juvenile visceral steatosis mice with systemic carnititne deficiency." Life Sci.64. 1137-1144 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Horiuchi M: "Secondary abnormality of carnitine biosynthesis results from carnitine reabsorptional system defect in juvenile visceral steatosis mice." Biochim.Biophys.Acta. 1362. 263-268 (1998)

    • Related Report
      1998 Annual Research Report

URL: 

Published: 1998-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi