2010 Fiscal Year Final Research Report
Molecular analysis of angiontensin II receptor inactivation by inverse agonists
| Project/Area Number |
20390218
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Chiba University |
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Principal Investigator |
AKAZAWA Hiroshi Chiba University, 医学系研究科, 特任講師(常勤) (20396683)
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| Co-Investigator(Renkei-kenkyūsha) |
KOMURO Issei 大阪大学, 医学系研究科, 教授 (30260483)
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| Project Period (FY) |
2008 – 2010
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| Keywords | シグナル伝達 / 循環器・高血圧 / 細胞・組織 |
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| Research Abstract |
Angiotensin II (AngII) type 1 (AT_1) receptor physically interacts with other mechanosensitive molecules, which implicates functional relevance of the mutual interactions in mechanosensation by AT_1 receptor. Multivalent interactions between an inverse agonist and the AT_1 receptor cooperate to stabilize the receptor in an inactive conformation in response to the distinct processes of AngII-independent activation. Constitutive activity of AT_1 receptor contributes to cardiac remodeling independently of AngII even in vivo, when AT_1 receptor is up-regulalted in the heart, and inverse agonism of AT_1 receptor blockers provides therapeutic effects in the prevention of cardiac remodeling induced by constitutive activity of AT_1 receptor.
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[Journal Article] Promotion of CHIP-mediated p53 degradation protects the heart from ischemic injury.2010
Author(s)
Naito AT, Okada S, Minamino T, Iwanaga K, Liu ML, Sumida T, Nomura S, Sahara N, Mizoroki T, Takashima A, Akazawa H, Nagai T, Shiojima I, Komuro I.
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Journal Title
Circ Res. 106
Pages: 1692-1702
Peer Reviewed
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[Journal Article] Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload.2010
Author(s)
Shimizu I, Minamino T, Toko H, Okada S, Ikeda H, Yasuda N, Tateno K, Moriya J, Yokoyama M, Nojima A, Koh GY, Akazawa H, Shiojima I, Kahn CR, Abel ED, Komuro I.
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Journal Title
J Clin Invest. 120
Pages: 1506-1514
Peer Reviewed
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[Journal Article] Cardiac mast cells cause atrial fibrillation through PDGF-A-mediated fibrosis in pressure-overloaded mouse hearts.2010
Author(s)
Liao CH, Akazawa H, Tamagawa M, Ito K, Yasuda N, Kudo Y, Yamamoto R, Ozasa Y, Fujimoto M, Wang P, Nakauchi H, Nakaya H, Komuro I.
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Journal Title
J Clin Invest. 120
Pages: 242-253
Peer Reviewed
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[Journal Article] PDK1 coordinates survival pathways and β-adrenergic response in the heart.2009
Author(s)
Ito K, Akazawa H, Tamagawa M, Furukawa K, Ogawa W, Yasuda N, Kudo Y, Liao CH, Yamamoto R, Sato T, Molkentin JD, Kasuga M, Noda T, Nakaya H, Komuro I.
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Journal Title
Proc Natl Acad Sci USA. 106
Pages: 8689-8694
Peer Reviewed
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