| 產品描述： | HSF1A is a cell-permeable activator of heat shock transcription factor 1 (HSF1). HSF1A also acts as a specific inhibitor of TRiC/CCT. Chaperonin TCP-1 ring complex (TRiC)/chaperonin containing TCP-1 (CCT) plays a pivotal role in toxin translocation and/or refolding |
| 靶點： |
HSF1;HSP |
| 體外研究： |
HSF1A protects cells from stress-induced apoptosis, binds TRiC subunits and inhibits TRiC activity without perturbation of ATP hydrolysis. Genetic inactivation or depletion of the TRiC complex results in human HSF1 activation and HSF1A inhibits the direct interaction between purified TRiC and HSF1 in vitro. Moreover, fluorescence anisotropy experiments using FITC coupled to HSF1A demonstrates that HSF1A-FITC binds to a purified Tcp1 subunit of TRiC with an affinity of approximately 600 nM. This is validated qualitatively via titration of purified Tcp1 into binding reactions containing 500 nM Biotin or HSF1A-Biotin. Quantification by counting the number of cell containing aggregates as a function of the total number of cells reveals that at HSF1A concentrations as low as 2 μM, a reduced number of aggregate-containing cells are observed. The fraction of cells containing aggregates continued to decrease in a dose-dependent manner such that pretreatment with 12 μM HSF1A resulta in ~20% of the cells exhibiting aggregates visible by fluorescence microscopy |
| 體內研究： |
HSF1A enhances HSF1 activity, stabilizes HSF1 expression and minimizes Doxorubicin (DOX)-induced cardiac damage. WKY rats are challenged with DOX (accumulated dose: 30?mg/kgw), and DOX combined with HSF1A (100?mg/kgw/day). Supplementation with HSF1A significantly elevates cardiac functions back to the levels of the control group. HSF1A has been shown to stimulate human HSF1 nuclear translocation, elevate protein chaperone expression and ameliorate protein misfolding and cell death in a neurodegenerative disease model. The echocardiographic results show that HSF1A also alleviates DOX-induced failures in cardiac function |
| 參考文獻： |
1. Neef DW, et al. A direct regulatory interaction between chaperonin TRiC and stress-responsive transcription factor HSF1. Cell Rep. 2014 Nov 6;9(3):955-66. 2. Neef DW, et al. Modulation of heat shock transcription factor 1 as a therapeutic target for small molecule intervention in neurodegenerative disease. PLoS Biol. 2010 Jan 19;8(1):e1000291. 3. Huang CY, et al. Doxorubicin attenuates CHIP-guarded HSF1 nuclear translocation and protein stability to trigger IGF-IIR-dependent cardiomyocyte death. Cell Death Dis. 2016 Nov 3;7(11):e2455. 4. Marcus Steinemann, et al. The chaperonin TRiC/CCT is essential for the action of bacterial glycosylating protein toxins like Clostridium difficile toxins A and B. Proc Natl Acad Sci U S A. 2018 Sep 18;115(38):9580-9585. |
| 溶解性： |
Soluble in DMSO |
| 保存條件： |
-20℃ |
| 配置溶液濃度參考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.442 ml |
12.209 ml |
24.419 ml |
| 5 mM |
0.488 ml |
2.442 ml |
4.884 ml |
| 10 mM |
0.244 ml |
1.221 ml |
2.442 ml |
| 50 mM |
0.049 ml |
0.244 ml |
0.488 ml |
|
| 注意： |
部分產品我司僅能提供部分信息，我司不保證所提供信息的權威性，僅供客戶參考交流研究之用。 |
上海工商
危險品化學品經營許可證（不帶存儲）
營業執照(三證合一)
北京