2002 Fiscal Year Final Research Report Summary
Redox Regulation of Signal Transduction Mechanism in the Heart
| Project/Area Number |
13470483
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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 |
Biological pharmacy
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| Research Institution | Kyushu University (2002)
The University of Tokyo (2001) |
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Principal Investigator |
KUROSE Hitoshi Kyushu University Pharmacology and Toxicology Professor, 大学院・薬学研究院, 教授 (10183039)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAO Tanku National Institute of Food Drug and Health Head, 所長(研究職) (30217971)
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| Project Period (FY) |
2001 – 2002
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| Keywords | reactive oxygen species / oxidative stress / cysteine residue / G protein / signaling molecule / intracellular mediator |
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| Research Abstract |
Reactive oxygen species (ROS) has been considered as an 'evil player' due to a strong reactivity. We have reported that trimeric G protein (G_i/G_0) is directly activated by one of ROS hydrogen peroxide (H_2O_2) in rat neonatal myocytes. Upon activation of G_i/G_0 by H_2O_2, Gβγis released from trimeric G_i/G_0 and the released Gβγ activates ERK to protect the cells against oxidative damage. We have now identified the amino acids that are modified by H_2O_2, and have found that the H_2O_2-mediated modification of cysteine residues located at 287 and 326 is necessary for activation of G_i. These results indicate that ROS can work as an intracellular mediator in the heart, and suggest that ROS generated by receptor stimulation can activate G_i and G_0. Other than the treatment of cells with H_2O_2, ROS was generated by receptor stimulation. Although angiotensin II stimulation generated ROS and induced MAP kinase activation, angiotensin II stimulation could not activate G_i and G_0. Therefore, we concluded that the amount of ROS is an important factor for activation of G protein. We have also found that the expression of peroxiredoxin II (PrxII) eliminates ROS from cells, and PrxII abolishes c-Jun NH_2-terminal kinase (JNK) activation without affecting ERK and p38 MAPK activation. It is concluded that angiotensin II activates specific signaling pathway leading to JNK activation. It also suggests that ROS can work as an intracellular mediator.
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[Publications] Hara Y., Wakamori M., Ishii M., Maeno E., Nishida M., Yoshida T., Yamada H., Shimizu S., Mori E., Kudoh J., Shimizu N., Kurose H., Okada Y., Imoto K., Mori Y.: "LTRPC2 Ca^<2+>-permeable channel activated by changes in redox status confers susceptibility to cell death"Mol. Cell. 9. 163-172 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Sugimoto Y., Fujisawa R., Tanimura R., Lattion, A. L., Cotecchia S., Tujimoto G., Nagao T., and Kurose H.: "β_1-Selective agonist (-)-1-(3,4-dimethoxyphenetylamino)-3-(3, 4-dihydroxy)-2-propanol [(-)-RO363] differentially interacts with key amino acids responsible for β_1-selective binding in resting and active states"J. Pharmacol. Exp. Ther.. 301. 51-58 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Arai K., Maruyama Y., Nishida Tanabe S., Takagahara S., Turner J. H., Kozasa T., Mori Y., Nagao T., and Kurose H.: "Differential requirement of Gα_<12>, Gα_<13>, Gα_q and Gβγ for endothelin-1-induced JNK and ERK activation"Mol. Pharmacol.. 63. 478-488 (2003)
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「研究成果報告書概要(欧文)」より
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