1997 Fiscal Year Final Research Report Summary
Development of Strategy of Molecular Cloning of Cardiac-Specific-Gene by use of Adriamycin
| Project/Area Number |
08557048
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Gunma University School of Medicine (1997)
The University of Tokyo (1996) |
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Principal Investigator |
KURABAYASHI Masahiko Gunma University School of Medicine Second Department of Internal Medicine Assistant Professor, 医学部, 講師 (00215047)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAOKI Kazuhide University of Tokyo Third Department of Internal Medicine Assistant Professor, 医学部, 講師 (70182409)
YAZAKI Yoshio University of Tokyo Third Department of Internal Medicine Professor, 医学部, 教授 (20101090)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Adriamycin / CARP / Cardiomyocytes / Hypertrophy / Oxidative Stress / Endothelium / Promoter / Transcription Factor |
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| Research Abstract |
CARP,a cardiac adriamycin response protein, has been identified as a nuclear protein whose expression is down-regulated in response to adriamycin. In this study, we sought to examine the link between the pathophysiological stress and the regulation of CARP gene expression to specifically test the hypothesis that CARP functions as a nuclear factor mediating genetic response to diverse stress in the heart. CARP expression markedly increased in pressure-overloaded hypertrophy of rat heart. CARP expression increased during rat development, which is in a sharp contrast to the concept that cardiac hypertrophy is accompanied by the reactivation of the "fetal" gene program. Consistent with pressure-depenedent regulation, CARP mRNA was present in greater abundance in left ventricle than in right ventricle. In Dahl salt sensitive rats which exhibits the transition from cardiac hypertrophy to heart failure in a salt dependent manner, CARP mRNA increased during the period of compensatoty cardiac hypertrophy but such an increase in CARP mRNA level was attenuated after overt heart failure developed. Intraperitoneal administration of low dose of lipopolysaccharides(LPS) in rats induced CARP expression in the heart whereas higher dose of LPS repressed its expression despite either equally increased the level of iNOS mRNA.Chronic intravenous injection of adriamycin in rabbits increased CARP mRNA levels in mild heart failure while decreased it when heart failure became severe as assessed by the downregulation of Ca-ATPase mRNA.These results suggest taht CARP expression is differentially regulated depending upon the magnitude of hemodynamic overload and CARP may play a role in regulating gene expression during cardiac adaptation and failure.
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[Publications] Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., etal.: "Mutation of the mouse klotho gene leads to a syndrome resembling ageing." Nature. 390. 45-51 (1997)
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[Publications] Suzuki, T., Katoh, H., Watanabe, M., Kurahayashi, M., Hiramori, K., Hori, S., Nobuyoshi, M., Tanaka, H., Kodama, K., Sato, H., Suzuki, S., Yazaki, Y., Nagai, R.: "A novel biochemical method for aortic dissection." Circulation. 93. 1244-1249 (1996)
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[Publications] Suzuki, t., Kim, H-S., Kurabayashi, M., Hamada, H., Fujii, H., Aikawa, M., Watanabe, M., Watanabe, N., Sakomura, Y., Yazaki, Y., Nagai, R.: "Preferential differentiation of P19 mouse embryonal carcinoma cells into smooth muscle cells ; use of retinoic acid and antisense against the central nervous system-specific POU transcription factor Brn-2." Circ.Res.78. 395-404 (1996)
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[Publications] Watanabe, M., Sakomura, Y., Kurabayashi, M., Manabe, I., Aikawa, M., Yazaki, Y., Nagai, R.: "Structure and characterization of the 5'-flanking region of the mouse smooth muscle myosin heavy chain SM1/2 gene" Circ.Res.78. 978-989 (1996)
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