| 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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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2002: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2001: ¥8,900,000 (Direct Cost: ¥8,900,000)
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| Keywords | reactive oxygen species / oxidative stress / cysteine residue / G protein / signaling molecule / intracellular mediator / 酸素毒性 / 細胞保護 / セリン変異体 |
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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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