Activation of redox signal by environmental quinones and regulation of the signal by reactive sulfur species
| Project/Area Number |
17K15489
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Environmental and hygienic pharmacy
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Abiko Yumi 筑波大学, 医学医療系, 助教 (80742866)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 電子受容体 / 9,10-フェナンスレンキノン / レドックスシグナル / PTP1B / パースルフィド / 芳香族炭化水素 / キノン / 9,10-フェナントラキノン / 活性酸素種 / PTP / イオウ化合物 |
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| Outline of Final Research Achievements |
Endogenous reactive oxygen species (ROS) activate epidermal growth factor receptor (EGFR) through oxidative modification of cysteine residue of protein tyrosine phosphatase (PTP) 1B, which is a sensor protein. Whereas an environmental air pollutant 9,10-phenanthraquinone (9,10-PQ) generates ROS due to its redox activity, whether or not 9,10-PQ can activate PTP1B/EGFR signal is still unclear. In this study, we clarified that 9,10-PQ-derived ROS activated EGFR through oxidative inactivation of PTP1B and that persulfhydration of Cys on PTP1B protectd the thiol from irreversible oxidation.
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| Academic Significance and Societal Importance of the Research Achievements |
大気成分中には発がん物質など種々の芳香属炭化水素が含まれ，光酸化や生体内での代謝によりキノン体に変換される．キノン体は反応生が高く9,10-PQのようにレドックス活性を有する物質も多いため，環境化学物質によるROSが内在性ROSを模倣してPTP1B/EGFRシグナルに代表されるレドックスシグナルを活性化することを明らかにしたことは予防医学や毒性学において有用な知見といえよう．また，パーイオウ化されたシステイン残基の可逆性が明らかとなり，レドックスシグナル伝達において酸化だけでなくパーイオウ化の関与も検討すべき課題であるといえよう．
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Report
(4 results)
Research Products
(29 results)
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[Journal Article] Control of Protein Function Through Oxidation and Reduction of Persulfidated States2020
Author(s)
E Doka, T Ida, M Dagnell, Y Abiko, N C Luong, N Balog, T Takata, B Espinosa, A Nishimura, Q Cheng, Y Funato, H Miki, J M Fukuto, J R Prigge, E E Schmidt, E S J Arner, Y Kumagai, T Akaike, P Nagy
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Journal Title
Sci Adv
Volume: 6
Issue: 1
Pages: 8358-8358
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] 1,4-Naphthoquinone activates the HSP90/HSF1 pathway through the S-arylation of HSP90 in A431 cells: Negative regulation of the redox signal transduction pathway by persulfides/polysulfides2017
Author(s)
Abiko Y, Sha L, Shinkai Y, Unoki T, Luong NC, Tsuchiya Y, Watanabe Y, Hirose R, Akaike T, Kumagai Y.
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Journal Title
Free Radic Biol Med
Volume: 104
Pages: 118-128
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] The obligatory role of the S-sulfuration in reversibility of PTP1B activity.2019
Author(s)
Abiko Y, Nho C. Luong, Jon M. Fukuto, Funato Y, Miki H, Doka E, Dagnell M., Ida T, Balog N., Espinosa B., Nishimura A, Prigge R. J, Schmidt E. E., Arner E. S. J., Akaike T., Nagy P., Kumagai Y.
Organizer
1st International Conference on Persulfide and Sulfur Metabolism in Biology and Medicine
Related Report
Int'l Joint Research
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