2003 Fiscal Year Final Research Report Summary
Activation of ERK during ischemia-reperfusion in lung transplantation.
| Project/Area Number |
14571268
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | THE University of Tokushima |
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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)
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| 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)
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| Project Period (FY) |
2002 – 2003
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| Keywords | lung transplantation / reperfusion / ischemia-reperfusion / preservation / protein tyrosine phosphorylation / mitogen-activated protein kinase / ERK |
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| 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.
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Research Products
(4 results)
