| Project/Area Number |
13670726
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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 | Nagasaki University |
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Principal Investigator |
TODA Genji Course of Medical and Dental Science, Graduate School of Biomedical Science, Lecturer, 大学院・医歯薬学総合研究科, 講師 (00253659)
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| Co-Investigator(Kenkyū-buntansha) |
YANO Katsusuke Course of Medical and Dental Science, Graduate School of Biomedical Science, Professor, 大学院・医歯薬学総合研究科, 教授 (50039864)
KONDO Takahito Course of Medical and Dental Science, Graduate School of Biomedical Science, professor, 大学院・医歯薬学総合研究科, 教授 (00158908)
IHARA Yoshito Course of Medical and Dental Science, Graduate School of Biomedical Science, Associate professor, 大学院・医歯薬学総合研究科, 助教授 (70263241)
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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 |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | calreticulin / cardiomyocyte / apoptosis / molecular chaperone |
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| Research Abstract |
Calreticulin is a ubiquitous Ca2+ binding protein, located in the endoplasmic reticulum. Calreticulin has been shown to be essential for cardiac development in mice, but the mechanism is not fully understood. To examine the biological role of calreticulin in cardiac differentiation, the calreticulin gene was introduced into rat cardiomyoblast H9c2 cells. Upon culture in a differentiation medium containing fetal calf serum (1%) and retinoic acid (10nM), cells transfected with the calreticulin gene were highly susceptible to apoptosis compared with controls. In the gene-transfected cells, protein kinase B/Akt signaling was significantly suppressed during differentiation. Furthermore, protein phosphatase 2A, a Ser/Thr protein phosphatase was significantly up-regulated, implying suppression of Akt signaling due to dephosphorylation of Akt by the up-regulated protein phosphatase 2A via regulation of Ca2+ homeostasis. Thus, overexpression of calreticulin promotes differntiation-dependent apoptosis in H9c2 cells by suppressing the Akt signaling pathway. These findings indicate a novel mechanism by which cytoplasmic Akt signaling is modulated to cause apoptosis by a resident protein of the endoplasmic reticulum, calreticulin.
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