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2003 Fiscal Year Final Research Report Summary

Activation of ERK during ischemia-reperfusion in lung transplantation.

Research Project

Project/Area Number 14571268
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionTHE University of Tokushima

Principal Investigator

SAKIYAMA Shoji  University of Tokushima, University hospital, senior assistant professor, 医学部・歯学部附属病院, 講師 (60291986)

Co-Investigator(Kenkyū-buntansha) MIYOSHI Takanori  University of Tokushima, School of Medicine, assistant professor, 医学部, 助手 (20346612)
KONDO Kazuya  University of Tokushima, School of Medicine, senior assistant professor, 医学部, 講師 (10263815)
MONDEN Yasumasa  University of Tokushima, School of Medicine, Professor, 医学部, 教授 (60028628)
KENZAKI Koichiro  University of Tokushima, University hospital, assistant professor, 医学部・歯学部附属病院, 助手 (70325265)
Project Period (FY) 2002 – 2003
Keywordslung transplantation / reperfusion / ischemia-reperfusion / preservation / protein tyrosine phosphorylation / mitogen-activated protein kinase / ERK
Research Abstract

1.Experiment in a rat lung transplant model.
Dramatic alterations of protein tyrosine phosphorylation have been found during the ischemia-reperfusion period of human lung transplantation. The object of the present study was to determine whether these changes exist in a rat single-lung transplant model. Lung transplantations were performed after 6 hours of cold ischemic preservation. In both iso-and allografts, the lung function of transplants was very well preserved. Protein tyrosine phosphorylation, protein tyrosine kinase and protein tyrosine phosphatase activities were decreased significantly after 2 hours of reperfusion. Src protein level and phosphorylation of p38 were reduced after 2 hours of reperfusion. This lung transplantation model is useful for studying ischemia-reperfusion injury.
MAPK activation in human lung transplant
The phosphorylation status of MAPK during ischemia-reperfusion in human lung transplant was examined. These transplantations were performed in Toronto General Hospital in Canada. Lung tissue biopsy was performed on 15 patients undergoing transplantation: after the cold ischemic preservation, after the warm ischemia (implantation) and after 1 h or 2 h reperfusion. The phosphorylation status of ERK, p38-MAPK, INK and MEK was examined with Western blotting. Phosphorylation of INK also significantly increased at lower levels. In contrast, phosphorylation of p38 had no significant changes. The increase in ERK phosphotylation was not associated with the activation of MEK, the up-stream kinase for ERK. Since MKP-3 protein levels correspond to its activity, we examined the protein expression of MKP-3 in these samples. Surprisingly, the MKP-3 protein level significantly increased after reperfusion. Therefore, the dramatic increase in ERK phosphorylation is not due to the inhibited expression of MKP-3.

  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Takehisa Y, Sakiyama S他: "Progressive increase of CD4(+)/CD45RC(-) lymphocytes after allograft rat lung transplantation : a marker of acute rejection."J Thorac Cardiovasc Surg. 124. 675-683 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakiyama S 他: "Ischemia-reperfusion decreases protein tyrosine phosphorylation and p38 mitogen-activated protein kinase phosphorylation in rat lung transplants."J Heart Lung Transplant. 22. 338-346 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takehisa Y, Sakiyama S, Uyama T, Sumitomo M, Tamaki M, Hino H, Takehisa M, Liu M, Kondo K, Monden Y.: "Progressive increase of CD4(+)/CD45RC(-) lymphocytes after allograft rat lung transplantation : a marker of acute rejection."J Thorac Cardiovase Surg.. 124(4). 675-683 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakiyama S, dePerrot M, Han B, Waddell TK, Keshavjee S, Liu M.: "Ischemia-reperfusion decreases protein tyrosine phosphorylation and p38 mitogen-activated protein kinase phosphorylation in rat lung transplants."J Heart Lung Transplant.. 22(3). 338-346 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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