1989 Fiscal Year Final Research Report Summary
Molecular analysis of the pathophysiology of heart disease
| Project/Area Number |
62440041
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | University of Tokyo |
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Principal Investigator |
YAZAKI Yoshio University of Tokyo, Medicine, Associate Professor, 医学部・第三内科(病), 助教授 (20101090)
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| Co-Investigator(Kenkyū-buntansha) |
KOMURO Issei University of Tokyo, Medicine, 医学部・第三内科(病), 医員
KURABAYASHI Masahiko University of Tokyo, Medicine, Associate, 医学部・第三内科(病), 助手 (00215047)
TSUCHIMOCHI Hidetsugu University of Tokyo, Medicine, Associate, 医学部・第三内科(病), 助手 (90197715)
YAMAOKI Kazuhide University of Tokyo, Medicine, Associate, 医学部・第三内科(病), 助手 (70182409)
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| Project Period (FY) |
1987 – 1989
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| Keywords | myosin isozyme / myosin heavy chain / myosin light chain / c-fos / c-myc / cardiac hypertrophy / myosin gene / oncogenes |
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| Research Abstract |
The process of enlargement of the heart due to overload involves a significant reconstitution of the organ including myocytes and intracellular constituents. We demonstrated the distribution of two types of cardiac myosin heavy chains (HCalpha and HCbeta) in the human heart using monoclonal antibodies. The ventricle comprised mainly HCbeta which has low ATPase activity, whereas the atrium was predominantly composed of HCalpha which has high ATPase activity. We also demonstrated isozymic transition of HCalpha to HCbeta in the human atrium and ventriele by hemodynamic overload, regarded as a compensatory mechanism to meet an increased demand in work.
To examine the molecular mechanism for the expression of these we have isolate human HCaloha and HCbeta cDNA clones from a fetal heart cDNA library. Comparison of the nucleotide and amino acid sequences deduced from the DNA between these cDNA clones showed 91 and 96% homology, respectively. Using HCalpha and HCbeta genespecific sequences, we demonstrated that the transition of HCalpha to HCbeta in the overloaded human heart was induced by the expression of HCbeta-gene.
To determine the role of cellular oncogenes in the process of cardiac growth and hypertrophy, we examined the expression pattern of eight cellular oncogenes during the developmental stage and pressure-overloaded hypertrophy of the rat heart by Northern blot analysis. c-fos, c-myc and c-Ha-ras were expressed in the heart in response to pressure overload and in a stage-specific manner, suggesting that these cellular oncogenes participate in the normal developmental process and hypertrophy of the heart. We also cloned the genes of which expression level was rapidly changed by pressure overload by differential hybridization technique. Our results suggest that clone 4 may be involved in the molecular mechanism for the development of cardiac hypertrophy due to overload.
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