| Project/Area Number |
17590247
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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 |
General medical chemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
YODOI Junji (2006) Institute for Virus Research Kyoto University, Professor, ウイルス研究所, 教授 (80108993)
近藤 則彦 (2005) 京都大学, ウイルス研究所, 助手 (50378949)
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| Co-Investigator(Kenkyū-buntansha) |
MASUTANI Hiroshi Institute for Virus Research Kyoto University, Associate Professor, ウイルス研究所, 助教授 (50252523)
淀井 淳司 京都大学, ウイルス研究所, 教授 (80108993)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | thioredoxin / redox regulation / lipid rafts / modified protein / ストレスシグナル / レドックス(酸化還元) |
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| Research Abstract |
Thioredoxi-1 (TRX) plays important roles on cellular signaling by controlling the redox state of cysteines residues in target proteins. TRX is released in response to oxidative stress and shows various biological functions also in extracellular environment. We have reported the mechanism of the internalization of TRX into cells.
Last year, Dr. Kondo revealed that TRX (TRX-C35), which the cysteine at residue 35 of active site of TRX was replaced with serine, binds rapidly to cell surface and is internalized into cells through lipid rafts in the plasma membrane. Since the internalization of TRX-C35 into cells was observed especially in virus-infected T cells or activated T cells, lipid rafts is considered to play important roles in TRX-C35 entry into cells. Meanwhile, TRX-C35 is a useful material to analyze TRX binding to cell surface or TRX uptake into cells.
This year, we examined the biological function of TRX-C35.
We examined an stress-induced apoptosis of Jurkat T cells triggered by anti-cancer agent cis-diammininedichloroplatinum (CDDP). The results show that the internalized TRX-C35 bound to endogenous TRX, resulting in the generation of intracellular reactive oxygen species (ROS) and enhanced CDDP-induced apoptosis via a ROS-mediated pathway involving apoptosis signal-regulating kinase-1 (ASK-1) activation.
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