2004 Fiscal Year Final Research Report Summary
Proteome analysis reveals molecular alternations of cardiac protein expression via Angiotensin-II in congestive heart failure
| Project/Area Number |
15590736
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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 | Shiga University of Medical Science |
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Principal Investigator |
WADA Atsuyuki Shiga University of Medical Science, Cardiovasculr Medicine, Associate Professor, 医学部, 講師 (10273400)
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| Co-Investigator(Kenkyū-buntansha) |
ISONO Takahiro Shiga University of Medical Science, Central Research Laboratory, Associate Professor, 医学部, 助教授 (20176259)
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| Project Period (FY) |
2003 – 2004
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| Keywords | proteomics / congestive heart failure / MALDI-TOF MS / alpha B crystallin / HSP27 / HSP 20 / phosphorylation |
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| Research Abstract |
As congestive heart failure(CHF) is a complex syndrome with many different underlying mechanisms of worsening of heart function, it is important to recognize global alternations in protein expression associated with the processes of CHF. The aim of our study was to use a proteomics approach to investigate global alternations in protein expression in tachycardia induced CHF dogs. We compared the two-dimensional electrophoresis(2-DE) protein patterns of left ventricular samples from the normal with those from failing myocardium. Differentially expressed cardiac proteins showed as many as 500 cardiac protein spots. Six of these spots were significantly upregulated in CHF compared to the normal group. These spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometric (MALDI-TOF MS) analysis as alpha B crystallin, heat shock protein(HSP) 20 and HSP27 which maintain both the morphological and functional integrity of the cardiomyocytes and increase tolerance against various types of stress. Since phosphorylation is one of the most important post-translational modifications, we evaluated whether the overexpressed HSPs were phosphorylated in CHF. Phosphoprotein staining and Western blotting demonstrated that the phosphorylated forms of these small HSPs significantly increased in CHF compared with the normal group. As for alpha B crystallin and HSP27, the phosphorylation at the serine(Ser)-59,Ser-78 and Ser-82 sites respectively were significantly upregulated in CHF. Our study suggests that proteomics studies can provide new insights into molecular mechanisms in CHF and phosphorylated small HSPs may contribute to preventing cardiac dysfunction.
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Research Products
(9 results)
