Project/Area Number |
24590159
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Environmental pharmacy
|
Research Institution | University of Tsukuba |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
KUMAGAI Yoshito 筑波大学, 医学医療系, 教授 (00250100)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 1,4-ナフトキノン / 親電子物質 / ストレス応答 / HSP/HSF1 / Keap1/Nrf2 / PTP1B/EGFR / 親電子シグナル / 細胞応答システム / 熱ショックタンパク質 / HSF1 |
Outline of Final Research Achievements |
1,4-Naphthoquinone (1,4-NQ), an environmental electrophile, is capable of covalently binding to cellular proteins, which has been recognized to be associated with not only its toxicity but also the activation of cellular signal transduction pathways for cellular protection against reactive chemicals. In this study, we prepared specific anti-1,4-NQ antibody and found that 1,4-NQ-mediated covalent modification of heat shock protein 90 (HSP90) causes activation of heat shock factor-1 (HSF1), resulting in protection against 1,4-NQ toxicity in A431 cells. Furthermore, Keap1/Nrf2 and PTP1B/EGFR pathways as well as HSP90/HSF1 pathway also found to play a role in protective response to 1,4-NQ toxicity.
|