2006 Fiscal Year Final Research Report Summary
Characterization of cardioprotective molecular mechanism via p38MAPK and new therapy for heart failure
| Project/Area Number |
17590732
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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 | OSAKA UNIVERSITY |
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Principal Investigator |
NISHIDA Kazuhiko Osaka University, Graduate School of Dentistry, Instructor, 歯学研究科, 助手 (90362681)
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| Co-Investigator(Kenkyū-buntansha) |
OTSU Kinya Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (20294051)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Cardioprotection / p38 MAP Kinase / Heart Failure |
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| Research Abstract |
The molecular mechanism for the transition from cardiac hypertrophy, an adaptive response to biomechanical stress, to heart failure is poorly understood. The mitogen-activated protein kinase p38α is a key component of stress response pathways in various types of cells. In response to pressure overload to the left ventricle, cardiac-specific p38a knockout mice developed cardiac dysfunction and heart dilatation. However, the conventional heterozygous p38α knockout mice exhibited resistance to ischemia-reperfusion insult. These results indicated that p38α plays a protective and promoting role in the regulation of cell death.
In order to characterize the molecular mechanism which determines the dual roles of p38 in the regulation of cell death and obtain a new target for heart failure, we examined aortic banding and isoproterenol treatment in the tamoxifen-inducible and cardiac-specific p38α knockout (inducible p38αCKO) mice.
We performed Tamoxifen injection before or after TAC in the inducible p38αCKO mice. We also performed Tamoxifen injection before or during treatment with isoproterenol. However, we obtained the same results that the inducible p38αCKO mice developed cardiac dysfunction in all condition, concluding that we can not characterize the molecular mechanism which determines the dual roles of p38 in the regulation of cell death in this experiment.
We examined the molecular mechanism of the myocardial cell death and obtained the result that apoptosis signal-regulating kinase 1 (ASK1) is involved not only in apoptosis but also in non-apoptotic cardiomyocyte death by ischemia-reperfusion. We reviewed that the role of ASK1 in cardiomyocyte apoptosis. We also reported that the antioxidant edaravone attenuates pressure overload-induced left ventricular hypertrophy and that presenilin 2 plays an important role in excitation-contraction coupling by interacting with cardiac ryanodine receptor in hearts.
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Research Products
(8 results)
