2011 Fiscal Year Final Research Report
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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| Keywords | 薬理学 |
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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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[Journal Article] Protein kinase A-mediated phosphorylation of TRPC6 channels underlies suppression of angiotensin II-induced vasoconstriction. Arterioscler2011
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 and Kurose H
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Journal Title
Thromb. Vasc. Biol
Volume: 31
Pages: 2278-2286
DOI
Peer Reviewed
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[Journal Article] TRPC3-mediated Ca2+ 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 and Nishida M
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Journal Title
Biochem. Biophys. Res. Commun
Volume: 409
Pages: 108-113
DOI
Peer Reviewed
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[Journal Article] Heterologous down-regulation of angiotensin type1 receptors by purinergic P2Y2 receptor stimulation through S-nitrosylation of NF-кB2011
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 and Kurose H
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Journal Title
Proc. Natl. Acad. Sci. USA
Volume: 108
Pages: 6662-6667
DOI
Peer Reviewed
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[Journal Article] Ca2+ influx and protein scaffolding via TRPC3 sustain PKCυハand ERK activation in B cells2010
Author(s)
Numaga T, Nishida M, Kiyonaka S, Kato K, Katano M, Mori E, Kurosaki T, Inoue R, Hikida M, Putney JW Jr, and Mori Y
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Journal Title
J. Cell Sci
Volume: 123
Pages: 927-938
DOI
Peer Reviewed
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[Journal Article] Inhibition of TRPC6 channel activity contributes to the anti-hypertrophic effects of natriuretic peptides-guanylyl cyclase-A signaling 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 and Nakao K
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Journal Title
Circ. Res
Volume: 106
Pages: 1849-1860
DOI
Peer Reviewed
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[Journal Article] Dual signaling pathways of arterial constriction by extracellular urine 5'-triphosphate in the rat2010
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 and Hirata M
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Journal Title
J. Pharmacol. Sci.
Volume: 115
Pages: 293-308
DOI
Peer Reviewed
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