Midkine plays a protective role against cardiac ischemia/reperfusion injury through a reduction of apoptotic reaction
| Project/Area Number |
15590734
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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 |
Circulatory organs internal medicine
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| Research Institution | Nagoya University |
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Principal Investigator |
HORIBA Mitsuru Nagoya University, Res.Inst.of Environ.Med., Assistant Professor, 環境医学研究所, 助手 (40345913)
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| Co-Investigator(Kenkyū-buntansha) |
KODAMA Itsuo Nagoya University, Res.Inst.of Environ.Med., Professor, 環境医学研究所, 教授 (30124720)
KADOMATSU Kenji Nagoya University, School of Medicine. Dept.of Biochemistry, Associate Professor, 大学院・医学系研究科, 助教授 (80204519)
MURAMATSU Takashi Nagoya University, School of Medicine. Dept.of Biochemistry, Professor, 大学院・医学系研究科, 教授 (00030891)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Midkine / myocardial injury / apoptosis / MK^<- / -> mice / 心筋虚血再灌流傷害 / ミッドカイン |
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| Research Abstract |
Midkine(MK) is a heparin-binding growth factor involved in diverse biological phenomena, e.g. neural survival, carcinogenesis and tissue repair. MK could have a protective action against ischemia/reperfusion(I/R) injury in the heart, because MK was shown to prevent apoptosis in cultured neurons and tumor cells. We investigated the issue in mice with and without genetic MK deletion. Myocardial injury following I/R was produced by transient occlusion of coronary arteries. In wild-type(WT) mice, MK expression was increased after I/R in the peri-infarct area. Infarct size/area at risk 24hr after I/R in MK^<-/-> mice was larger than WT (58% vs.31%). TUNEL-positive myocyte population in the peri-infarct area in MK^<-/-> was higher than WT. Left ventricular function after I/R was hampered more seriously in MK^<-/-> than WT. Supplemental application of MK to LV of MK^<-/-> at the time of I/R resulted in a reduction of the infarct size. Exogenous application of MK to cultured cardiomyocytes subjected to hypoxia/reoxygenation caused an upregulation of Bcl-2 in association with a reduction of apoptosis. We conclude that MK plays a protective role against I/R injury most likely through a prevention of apoptotic reaction. MK is a potentially important new molecular target for the treatment of ischemic heart disease.
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Report
(3 results)
Research Products
(8 results)
