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1994 Fiscal Year Final Research Report Summary

Hyperglycemia and atherosclerosis : Radical scavenger dysfunction and abnormal gene expression in endothelial cells

Research Project

Project/Area Number 05670854
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionSHIGA UNIVERSITY OF MEDICAL SCIENCE

Principal Investigator

KASHIWAGI Atsunori  THIRD DEPARTMENT OF MEDICINE,SHIGA UNIVERSITY OF MEDICAL SCIENCE,ASSISTANT PROFESSOR, 医学部, 講師 (20127210)

Co-Investigator(Kenkyū-buntansha) MAEGAWA Hiroshi  THIRD DEPARTMENT OF MEDICINE,SHIGA UNIVERSITY OF MEDICAL SCIENCE,INSTRUCTOR, 医学部, 助手 (00209363)
Project Period (FY) 1993 – 1994
KeywordsDiabetes mellitus / Aging / Hyperglycemia / Endothelial cells / Oxidative stress / ICAM-1 / Oxidative LDL / Glutathione redox cycle
Research Abstract

It has been well known that abnormal production and degradation of active oxygen radicals in vascular cells are major factors which can induce accelerated atherosclerosis in aging and diabetes mellitus. Particularly, we have shown that radical scavenger function is impaired in cultured endothelial cells exposed to high glucose condition. Furthermore, the increased oxidative stress in high glucose condition can induce activation of endothelial cell gene expression. The following vascular endothelial cell dysfunction was studied in the present study.
1) Impaired activation of pentose phosphate pathway and dysfunction of glutathione redox (GR) cycle in endothelial cells exposed to high glucose medium.
We reported that GR cycle was dccreased by 50% in endothelial cells exposed to high glucose medium (Kashiwagi et al Diabetes 1992, Kashiwagi et al. Diabetologia 1994, Asahina et al. Diabetes 1995). These abnormal GR cycle was also found in acidosis (Ikebuchi et al Metabolism, 1993) and was rev … More ersed by the treatment of either radical scavenger (Kashiwagi et al. Diabetes 1991,1991) or pyruvate to endothelial cells (Kashiwagi et al. Am J Physiol. in submission).
2) Endothelial cell activation in high glucose condition
Specific ICAM-1 expression in endothelial cells was induced as high glucose-specific and concentration-dependent manners and resulted in increased adhesion of monocytes to endothelial cells (Taki et al. Atheroscleresis in submission). The activation of endothelial cell function in high glucose condition was mediated via hyperosmolar effect and was not mediated by oxidative stress.
3) Oxidized LDL and Lysophosphatidylcholine and endothelial cell gene expression
Oxidized LDL and a main component lysophosphatidylcholine (LPC) can induce MCP-1 gene expression in endothelial cells (Takahara et al, Metabolism, in submission). This effect was mediated by activation of PKC.
[In summary] Metabolic abnormalities in diabetes (hyperglycemia, hyperosmolarity, acidosis, lipid oxidation) can induce profound effects on various gene expression of endothelial cells which indicate activation of endothelial cells resulting in accelerated interaction between monocytes and endothelial cells. The interaction may be an initial event of early atherogenesis in diabetes. To prevent aging of vascular tissue and atherosclerosis, clinical studies to prevent in vivo oxidative stress in diabetes using antioxidant drugs will be the future projects. Less

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Ikebuchi, M.: "Effcct of medium pll on glutathione redox cycle in cultured human umbilical vein endothelial cells." Metabolism. 42. 1121-1126 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] kashiwagi, A: "An insufficient hexose monophosphate shunt activity as a cause of abnormal radical scavenging function endothelial cells cultured in high glucose media." Diabetes. 41. 18A (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] kashiwagi, A.: "Abnormal glutathione metabolism and increased cytotoxicity caused by H202 in human umbilical vein endothelial cells cultured in high glucose medium." Diabetologia. 37. 264-269 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takagi, Y: "Significance of fructose autoxidation in protein oxidation and fromation of advanced glycation end product." J Diabetic Coml. (In press). (1995)

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      「研究成果報告書概要(和文)」より
  • [Publications] Asahina, T.: "Impaired activation of glucose oxidation and NADPH supply in human endothelial cells exposed to H202 in high glucose medium." Diabetes. (In press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] kashiwagi, A.: "Glucose metabolism and radical scavenger dysfunction in endothelial cells." Diabetes. (Supplement)(In press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] kashiwagi, A.: "Recent advances in endothelial cell dysfunction in diabetes." churchill Livingstone, 286 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] kashiwagi, A.: "Diabetes" Elsevier Science Publisher, 679-682 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikebuchi, M., Kashiwagi, A,Asahina, T., Tanaka, Y., Takagi, Y., Nishio, Y., Hidaka, H., Kikkawa, R., and Shigeta, Y.: "Effect of medium pH on glutathione redox cycle in cultured human umbilical vein endothelial cells." Metabolism. 42. 1121-1126 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kashiwagi, A., Asahina T,Nishio Y,Ikebuchi M,Tanaka Y,Shigeta Y.: "An insuficient hexose monophosphate shunt activity as a cause of abnormal radical scavenging function in endothelial cells cultured in high glucose media." Diabetes. 41. 18 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kashiwagi, A., Asahina M,Ikebuchi M., Tanaka Y., Takagi Y., Nishio Y., Kikkawa R., Shigeta Y.: "Abnormal glutathione metabolism and increased cytotoxicity caused by H_2O_2 in human umbilical vein endothelial cells cultured in high glucose medium" Diabetologia. 37. 264-269 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takagi, Y., Kashiwagi, A., Tanaka, Y., Asahina Y., Kikkawa R., Shigeta Y.: "Significance of fructose autooxidation in protein oxidation and formation of advanced glycation ent product" J Diabetic Compl. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Asahina T,Kashiwagi A.Nishio Y,Ikebuchi M,Harada N,Tanaka Y,Takagi Y,Saeki Y,Kikkawa R,Shigeta Y: "Impaired activation of glucose oxidation and NADPH supply in human endothelial cells exposed to H2O2 in high glucose medium." Diabetes. (In press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kashiwagi A,Asahina T,Nishio Y,Ikebuchi M,Tanaka Y,Kikkawa R,Shigeta Y.: "Glucose metabolism and radical scavenger dysfunction in endothelial cells." Diabetes (Supplement). (In press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kashiwagi A,Kikkawa R.: Abnormal glutathione redox cycle in cultured human endothelial cells for the pathogenesis of diabetic vascular complication. Diabetes 1991 ed by H.Rifkin, Colwell JA,Taylor SI,Elsevier Science Publisher. 679-682 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kashiwagi A,Shigeta Y.: Yukio Shigeta Churchill Livingstone. Glucose metabolism in endothelial cells. Recent advances in endothelial cell dysfunction in diabetes. ed by George L.King, 3-15 (1994)

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      「研究成果報告書概要(欧文)」より

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Published: 1996-04-15  

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