Study on the role of receptor-activated cation channel TRPC3 in cardiac remodeling
| Project/Area Number |
22689003
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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 |
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥26,650,000 (Direct Cost: ¥20,500,000、Indirect Cost: ¥6,150,000)
Fiscal Year 2011: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2010: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
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| Keywords | 薬理学 / 心不全 / イオンチャネル / カルシウム / 受容体 |
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| Research Abstract |
Structural remodeling of the heart induced by chronic hypertension or ischemia is a major cause for cardiac dysfunction. We have previously reported that diacylglycerol-activated transient receptor potential canonical channels(TRPC3 and TRPC6) mediate pressure overload-induced cardiac hypertrophy invivo. We here focused on the fact that TRPC6 channel activities are negatively regulated by Thr69 phosphorylation, and found that inhibition of PDEs or atrial natriuretic peptide suppresses cardiac hypertrophy and hypertension through TRPC6 inhibition. Notably, TRPC6 proteins formed a protein signaling complex with PKA and PDE3 in vascular smooth muscle cells. Furthermore, TRPC3 interacts with protein kinase C dependently on TRPC3-mediated Ca2+ influx, leading to production of reactive oxygen species via activation of NADPH oxidase, resulting in development of cardiac remodeling, such as hypertrophy and fibrosis. These results strongly suggest that formation of TRPC3/6 protein signaling complex plays a pivotal role in cardiac remodeling.
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Report
(3 results)
Research Products
(60 results)
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[Journal Article] Protein kinase A-mediated phosphorylation of TRPC6 channels underlies suppression of angiotensin II-induced vasoconstriction2011
Author(s)
Nishioka K, Nishida M, Ariyoshi M, Saiki S, Jian Z, Hirano M, Nakaya M, Sato Y, Kita S, Iwamoto T, Hirano K, Inoue R, Kurose H
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Journal Title
Arterioscler.Thromb.Vasc.Biol.
Volume: 31
Issue: 10
Pages: 2278-2286
DOI
Related Report
Peer Reviewed
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[Journal Article] TRPC3-mediated Ca^<2+> influx contributes to Rac1-mediated production of reactive oxygen species in MLP-deficient mouse hearts2011
Author(s)
Kitajima N, Watanabe K, Morimoto S, Sato Y, Kiyonaka S, Hoshijima M, Ikeda Y, Nakaya M, Ide T, Mori Y, Kurose H, Nishida M
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Journal Title
Biochem.Biophys.Res.Commun.
Volume: 409
Issue: 1
Pages: 108-113
DOI
Related Report
Peer Reviewed
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[Journal Article] Heterologous down-regulation of angiotensin type1 receptors by purinergic P2Y_2 receptor stimulation through S-nitrosylation of NF-κB2011
Author(s)
Nishida M, Ogushi M, Suda R, Toyotaka M, Saiki S, Kitajima N, Nakaya M, Kim K-M, Ide T, Sato Y, Inoue K, Kurose H
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Journal Title
Proc.Natl.Acad.Sci.USA.
Volume: 108
Issue: 16
Pages: 6662-6627
DOI
Related Report
Peer Reviewed
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[Journal Article] Dual Signaling Pathways of Arterial Constriction by Extracellular Uridine 5'-Triphosphate in the Rat2011
Author(s)
Sugihara M, Morita H, Matsuda M, Umebayashi H, Kajioka S, Ito S, Nishida M, Inoue R, Futatsuki T, Yamazaki J, Mori Y, Inoue R, Ito Y, Abe K, Hirata M
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Journal Title
Journal of Pharmacological Sciences
Volume: 115
Issue: 3
Pages: 293-308
DOI
NAID
ISSN
1347-8613, 1347-8648
Related Report
Peer Reviewed
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[Journal Article] Pertussis toxin upregulates angiotensin type 1 receptors through Toll-like receptor 4 -mediated Racactivation2010
Author(s)
Nishida M, Suda R, Nagamatsu Y, Tanabe S, Onohara N, Nakaya M, Kanaho Y, Shibata T, Uchida K, Sumimoto H, Sato Y, Kurose H
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Journal Title
J. Biol. Chem
Volume: 285
Issue: 20
Pages: 15268-15277
DOI
Related Report
Peer Reviewed
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[Journal Article] Inhibition of TRPC6 channel activity contributes to the anti-hypertrophic effects of natriuretic peptides-guanylyl cyclase-Asignaling in the heart2010
Author(s)
Kinoshita H, Kuwahara K, Nishida M, Jiang Z, Rong X, Kiyonaka S, Kuwabara Y, Kurose H, Inoue R, Mori Y, Li Y, Nakagawa Y, Usami S, Fujiwara M, Yamada Y, Minami T, Ueshima K & Nakao K
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Journal Title
Circ. Res.
Volume: 106
Issue: 12
Pages: 1849-1860
DOI
Related Report
Peer Reviewed
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[Journal Article] Ca^<2+> influx and protein scaffolding via TRPC3 sustain PKCβ 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
Journal of Cell Science
Volume: 123
Pages: 927-938
Related Report
Peer Reviewed
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[Journal Article] Inhibition of TRPC6 channel activity contributes to the anti-hypertrophie effects of natriuretic peptides-guanylyl cyclase-A signaling in the heart.2010
Author(s)
Kinoshita H, Kuwahara K, Nishida M, Jiang Z, Rong X, Kiyonaka S, Kuwabara Y, Kurose H, Inoue R, Mori Y, Li Y, Nakagawa Y, Usami S, Fujiwara M, Yamada Y, Minami T, Ueshima K, Nakao K
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Journal Title
Circulation Research
Volume: 106
Pages: 1849-1860
Related Report
Peer Reviewed
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[Journal Article] Dual signaling pathways of arterial constriction by extracellular urine 5-triphosphate in the rat.2010
Author(s)
Sugihara M, Morita H, Matsuda M, Umebayashi H, Kajioka S, Ito S, Nishida M, Inoue R, Futatsuki T, Yamazaki J, Mori Y, Inoue R, Ito Y, Abe K, Hirata M.
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Journal Title
The Journal of Pharmacological Sciences
Volume: (In press)
Related Report
Peer Reviewed
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