Project/Area Number |
22390049
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General pharmacology
|
Research Institution | Hiroshima University |
Principal Investigator |
SAKAI Norio 広島大学, 大学院・医歯薬保健学研究院, 教授 (70263407)
|
Co-Investigator(Kenkyū-buntansha) |
HIDE Izumi 広島大学, 大学院・医歯薬保健学研究院, 助教 (20253073)
TANAKA Shigeru 広島大学, 大学院・医歯薬保健学研究院, 助教 (20512651)
SEKI Takahiro 広島大学, 大学院・医歯薬保健学研究院, 助教 (50335650)
|
Project Period (FY) |
2010 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2012: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2010: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
|
Keywords | ケミカルシャペロン シャペロン介在性オートファジー / セロトニントランスポーター / γPKC / 膜輸送 / ケミカルシャペロン / 脳虚血 / うつ病 / 神経変性疾患 / 小脳長期抑圧 / セロトニントランスポータ / シャペロン介在性オートファジー / 低酸素負荷 |
Research Abstract |
(1) Congo red inhibited the aggregate formation of mutant ・PKC, which caused spinocerebellar ataxia type 14 (SCA14), thereby, the cytotoxicity of SCA14 mutant ・PKC was reduced. (2) It is believed that 30 % of proteins are degraded by the chaperone-mediated autophagy (CMA). We developed the fluorescent-based probe, HaloTag-fused GAPDH, which can evaluate the cellular activity of CMA in single cell level. Using this probe, we demonstrated that CMA is inhibited in cells expressing SCA14 mutant ・PKC. (3) We revealed that 4-phenylbutylate (4-PBA), a chemical chaperone, increased the serotonin uptake activity of serotonin transporter (SERT) probably by accelerating SERT membrane trafficking.
|