2004 Fiscal Year Final Research Report Summary
Molecular biological studies on the mechanisms of the intrinsic cardioprotection system
| Project/Area Number |
15591640
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Nagasaki University |
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Principal Investigator |
TOMIYASU Shiro Nagasaki University, University Hospital of Medicine and Dentistry, Assistant Professor, 医学部・歯学部附属病院, 講師 (90244061)
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| Co-Investigator(Kenkyū-buntansha) |
CHO Sungsam Nagasaki University, University Hospital of Medicine and Dentistry, Research Associate, 医学部・歯学部附属病院, 助手 (90325655)
MAEKAWA Takuji Nagasaki University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (10336167)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Cardioprotection / Antioxidant / Glutaredoxin / Akt / Redox / Apoptosis |
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| Research Abstract |
Although the role of oxidative stress in cardiovascular disease is well established, the protective mechanisms of antioxidants remain poorly defined. The members of thiol-disulfide oxidoreductases act as cytoprotective antioxidants. One of the most important thiol-disulfide oxidoreductases is glutaredoxin (GRX).
We demonstrated that overexpression of GRX protected cells from hydrogen peroxide (H_2O_2)-induced apoptosis by regulating the redox state of Akt. Akt was transiently phosphorylated, dephosphorylated, and then degraded in cardiac H9c2 cells undergoing H_2O_2-induced apoptosis. Under stress, Akt underwent disulfide・bond formation between Cys297 and Cys311 and dephosphorylation in accordance with an increased association with protein phosphatase 2A (PP2A). Overexpression of GRX protected Akt from H_2O_2-induced oxidation and suppressed recruitment of PP2A to Akt, resulting in a sustained phosphorylation of Akt and inhibition of apoptosis. This effect was reversed by cadmium, an inhibitor of GRX. Thus, GRX plays an important role in cardioprotection by protecting cells from apoptosis through the regulation of the redox state of Akt.
Now, we are investigating the redox regulation of glyceraldehyde-3-phosphate dehydrogenase by GRX.
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Research Products
(8 results)
