| Project/Area Number |
13670733
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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 | Yokohama City University School of Medicine |
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Principal Investigator |
UMEMURA Satoshi Yokohama City University School of Medicine, Dept. of Medicine II, Yokohama City Univ. Sch. Of Med., Professor, 第二内科学教室, 教授 (00128589)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Atsushi Yokohama City University School of Medicine, Dept. of Molecular Biology, Yokohama City Univ. Sch. Of Med., Assistant Professor, 第二生化学教室, 講師 (00264606)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | PKC / atypical PKC / ASIP / Signal Transduction / Hypertrophy / Heart Failure / Growth Factor / Cardiomyocyte |
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| Research Abstract |
Protein Kinase C (PKC) signaling pathway is involved in a variety of biological functions. Since activation of PKC pathway has been implicated in the development of cardiomyocyte hypertrophy, inhibition of this pathway would be an attractive target for the suppression of cardiomyocyte hypertrophy. Previous reports suggest that conventional PKC and novel PKC cause hypertrophic responses. We have recently focused our studies of PKC on atypical PKC, the third class of PKC family which is TPA and Ca2+insensitive and atypical PKC specific interacting protein (ASIP).
EGF are known to induce hypertrophic responses in cardiomyocytes, and by utilizing two PKC inhibitors showing species-dependent specificity, we suggested the possible involvement of atypical PKC in EGF signaling in the heart. We examined the cardiac expression of individual PKC isoforms at the cardiac hypertrophy stage and the heart failure stage in Dahl salt-sensitive rats by Western blot analysis. The *xpressions of PKCα, β and δ increased at the cardiac hypertrophy stage and remained the elevated at the heart failure stage. On the other hand, the expression of PKC_ε and aPKCs increased at the cardiac hypertrophy stage, but this increase tended to decline at the congestive heart failure stage. These results suggest that there are two groups of PKC isoforms. Several reports suggest that PKC_α, β and δ are involved in the development of cardiac hypertrophy and heart failure and that PKC_ε plays a role in the physiological hypertrophic response and cardioprotective actions.
These facts might indicate that all PKC isoforms (PKCα, β, δ, ε and aPKCs) expressed in the heart had similar function at the cardiac hypertrophy stage but two groups of PKC isoforms (PKCα, β, δand PKC_ε, aPKCs) had different function at the congestive heart failure stage.
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