Roles of Heterotrimeric GTP-Binding Proteins in the Progression of Heart Failure
Abstract.: Heart failure is a major cause of death in developed countries, and the development of an epoch-making cure is desired from the viewpoint for improving the quality of life and reducing the medical cost of the patient. The importance of neurohumoral factors, such as angiotensin (Ang) II an...
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| Format: | Article |
| Language: | English |
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Elsevier
2011-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S134786131930653X |
| _version_ | 1819265161802809344 |
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| author | Motohiro Nishida |
| author_facet | Motohiro Nishida |
| author_sort | Motohiro Nishida |
| collection | DOAJ |
| description | Abstract.: Heart failure is a major cause of death in developed countries, and the development of an epoch-making cure is desired from the viewpoint for improving the quality of life and reducing the medical cost of the patient. The importance of neurohumoral factors, such as angiotensin (Ang) II and catecholamine, for the progression of heart failure has been supported by a variety of evidence. These agonists stimulate seven transmembrane-spanning receptors that are coupled to heterotrimeric GTP-binding proteins (G proteins). Using specific pharmacological tools to assess the involvement of G protein signaling pathways, we have revealed that α subunit of Gq (Gαq) activates Ca2+-dependent hypertrophic signaling through diacylglycerol-activated transient receptor potential canonical (TRPC) channels (TRPC3 and TRPC6: TRPC3/6). In contrast, activation of Gα12 family proteins in cardiomyocytes confers pressure overload–induced cardiac fibrosis via stimulation of purinergic P2Y6 receptors induced by extracellular nucleotides released from cardiomyocytes. In fact, direct or indirect inhibition of TRPC3/6 or P2Y6 receptors attenuates pressure overload–induced cardiac dysfunction. These findings will provide a new insight into the molecular mechanisms underlying pathogenesis of heart failure. Keywords:: heart failure, fibrosis, G protein, transient receptor potential channel, purinergic P2Y6 receptor |
| first_indexed | 2024-12-23T20:40:59Z |
| format | Article |
| id | doaj.art-36e4cde4d7094ea8975001c9d0858c39 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-23T20:40:59Z |
| publishDate | 2011-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-36e4cde4d7094ea8975001c9d0858c392022-12-21T17:31:56ZengElsevierJournal of Pharmacological Sciences1347-86132011-01-01117115Roles of Heterotrimeric GTP-Binding Proteins in the Progression of Heart FailureMotohiro Nishida0Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Corresponding author. nishida@phar.kyushu-u.ac.jpAbstract.: Heart failure is a major cause of death in developed countries, and the development of an epoch-making cure is desired from the viewpoint for improving the quality of life and reducing the medical cost of the patient. The importance of neurohumoral factors, such as angiotensin (Ang) II and catecholamine, for the progression of heart failure has been supported by a variety of evidence. These agonists stimulate seven transmembrane-spanning receptors that are coupled to heterotrimeric GTP-binding proteins (G proteins). Using specific pharmacological tools to assess the involvement of G protein signaling pathways, we have revealed that α subunit of Gq (Gαq) activates Ca2+-dependent hypertrophic signaling through diacylglycerol-activated transient receptor potential canonical (TRPC) channels (TRPC3 and TRPC6: TRPC3/6). In contrast, activation of Gα12 family proteins in cardiomyocytes confers pressure overload–induced cardiac fibrosis via stimulation of purinergic P2Y6 receptors induced by extracellular nucleotides released from cardiomyocytes. In fact, direct or indirect inhibition of TRPC3/6 or P2Y6 receptors attenuates pressure overload–induced cardiac dysfunction. These findings will provide a new insight into the molecular mechanisms underlying pathogenesis of heart failure. Keywords:: heart failure, fibrosis, G protein, transient receptor potential channel, purinergic P2Y6 receptorhttp://www.sciencedirect.com/science/article/pii/S134786131930653X |
| spellingShingle | Motohiro Nishida Roles of Heterotrimeric GTP-Binding Proteins in the Progression of Heart Failure Journal of Pharmacological Sciences |
| title | Roles of Heterotrimeric GTP-Binding Proteins in the Progression of Heart Failure |
| title_full | Roles of Heterotrimeric GTP-Binding Proteins in the Progression of Heart Failure |
| title_fullStr | Roles of Heterotrimeric GTP-Binding Proteins in the Progression of Heart Failure |
| title_full_unstemmed | Roles of Heterotrimeric GTP-Binding Proteins in the Progression of Heart Failure |
| title_short | Roles of Heterotrimeric GTP-Binding Proteins in the Progression of Heart Failure |
| title_sort | roles of heterotrimeric gtp binding proteins in the progression of heart failure |
| url | http://www.sciencedirect.com/science/article/pii/S134786131930653X |
| work_keys_str_mv | AT motohironishida rolesofheterotrimericgtpbindingproteinsintheprogressionofheartfailure |