The molecular mechanism of oxidative stress-inducible NF-κB activation---role of tyrosine kinasesignaling
| Project/Area Number |
16590066
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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 |
Biological pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Sciences |
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Principal Investigator |
HAYAKAWA Makio Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Associate Professor, 薬学部, 助教授 (30198824)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | oxidative stress / reactive oxygen species / tyrosine kinase / NF-κB / Abl / EGF receptor / A431 / IκB kinase / Abl / reactive oxygen species / tyrosine phosphorylation / phosphatase / phosphatidylinositol-3-kinase / PTEN / hydrogen peroxide / Akt |
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| Research Abstract |
Oxidative stress is known to activate NF-κB in certain types of cells. However, the molecular mechanism how oxidative stress induces NF-κB activation is still unclear. In this study, we found that hydrogen peroxide significantly induced NF-κB activation in human epidermoid carcinoma cell line A431 overexpressing EGF receptor. Interestingly, A431 cells respond to EGF in terms of NF-κB activation. EGF-induced NF-κB activation requires tyrosine kinase activity of EGF receptor, while hydrogen peroxide-induced NF-κB activation does not. Both EGF and hydrogen peroxide activate "canonical NF-κB activating pathway" in which the activation of IκB kinase leads to the phosphorylation of IκB resulting in the liberation of NF-κB dimer composed of p65 and p50 through the proteasomal degradation of IκB. The studies using pharmacological inhibitors revealed that the involvements of Src family tyrosine kinases, PKC isoforms, and PKD are negligible, whereas Abl tyrosine kinase is a possible candidate for EGF- and hydrogen peroxide-induced NF-κB activation. In order to fully understand the molecular mechanism of oxidative stress responsive NF-κB activation, how Abl kinase is activated downstream of oxidative stress, and how it activates IκB kinase must be clarified.
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Report
(3 results)
Research Products
(1 results)
