Analysis of G protein signaling pathways involved in the development of heart failure and discovery of the novel therapeutic target.
| Project/Area Number |
19689003
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyushu University |
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Principal Investigator |
NISHIDA Motohiro Kyushu University, 大学院・薬学研究院, 准教授 (90342641)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000)
Fiscal Year 2009: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2008: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2007: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
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| Keywords | 薬理学 / 心不全 / シグナル伝達 / G蛋白質 / カルシウム / イオンチャネル / チャネル / 心肥大 / 線維化 / 受容体 / TRP / 圧負荷 / G 蛋白質 / Ca ^<2+>チャネル / transient receptor potential |
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| Research Abstract |
We focused on the roles of heterotrimeric G proteins coupling with receptors on the plasma membrane, and found that Gq protein singaling participates in the development of myocardial hypertrophy while G12 protein signaling participates in the development of cardiac fibrosis. In addition, we identified that TRPC channels mediate Gq-induced activation of Ca2+ signaling, and P2Y6 receptor triggers activation of G12 protein signaling. Furthermore, we found that inhibition of these targets improves heart failure in in vivo mouse hearts.
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Report
(4 results)
Research Products
(89 results)
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[Journal Article] Ca2+ influx and protein scaffolding via TRPC3 sustain PKCb and ERK activation in B cells.2010
Author(s)
Numaga T, Nishida M, Kiyonaka S, Kato K, Katano M, Mori E, Kurosaki T, Inoue R, Hikida M, Putney JW Jr, Mori Y
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Journal Title
J Cell Sci. 123
Pages: 927-938
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[Journal Article] Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound.2009
Author(s)
Kiyonaka S, Kato K, Nishida M, Mio K, Numaga T, Sawaguchi Y, Yoshida T, Wakamori M, Mori E, Numata T, Ishii M, Takemoto H, Ojida A, Watanabe K, Uemura A, Kurose H, Morii T, Kobayashi T, Sato Y, Sato C, Hamachi I, Mori Y
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Journal Title
Proc Natl Acad Sci USA. 106
Pages: 5400-5405
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[Journal Article] Keap1 regulates the constitutive expression of GST A1 during differentiation of Caco-2 cells.2008
Author(s)
Kusano Y, Horie S, Shibata T, Satsu H, Shimizu M, Hitomi E, Nishida M, Kurose H, Itoh K, Kobayashi A, Yamamoto M, Uchida K.
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Journal Title
Biochemistry 47
Pages: 6169-77
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[Journal Article] A food-derived synergist of NGF signaling: Identification of protein tyrosine phosphatase 1B as a key regulator of NGF receptor-initiated signal transduction.2008
Author(s)
Shibata T, Nakahara H, Kita N, Matsubara Y, Han C, Morimitsu Y, Iwamoto N, Kumagai Y, Nishida M, Kurose H, Aoki N, Ojika M, Uchida K.
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Journal Title
J Neurochem. 107
Pages: 1248-1260
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[Journal Article] P2Y_6 Receptor-Gα_<12/13> Signaling in Cardiomyocytes Triggers Pressure Overload-induced Cardiac Fibrosis.2008
Author(s)
Nishida M, Sato Y, Uemura A, Narita Y, Tozaki-Saitoh H, Nakaya M, Ide T, Suzuki K, Inoue K, Nagao T, Kurose H.
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Journal Title
EMBO J 27
Pages: 3104-3115
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