Activation of NRF2 Signaling in HEK293 Cells by a First-in-Class Direct KEAP1-NRF2 Inhibitor
作者： Xia Wen , Gabriell Thorne , Longqin Hu , Melanie S. Joy , Lauren M. Aleksunes
DOI: 10.1002/JBT.21693
关键词:
摘要: Under basal conditions, the antioxidant transcription factor nuclear (erythroid-derived 2)-like 2 (NRF2) is bound to Kelch-like ECH-associated protein 1 (KEAP1) and targeted for proteasomal degradation in cytoplasm. In response cellular injury or chemical treatment, NRF2 dissociates from KEAP1 activates of protective genes defends against injury. LH601A a first-in-class direct inhibitor KEAP1-NRF2 protein-protein interaction. The purpose this study was determine whether signaling human kidney cells. Human embryonic 293 (HEK293) cells were treated with indirect activator, sulforaphane (SFN) 6 16 h. SFN upregulated target heme oxygenase-1 (HO-1) (two- sevenfold), thioredoxin (TRX1) (twofold) NAD(P)H quinone oxidoreductase (NQO1) mRNAs (twofold). Both compounds also elevated HO-1 TRX1 expression. Since activation can protect tissues injury, LH601A, interaction may be used defend and/or diseases.
sci-hub.se 参考文章(22)
Sadagopan Magesh, Yu Chen, Longqin Hu, Small molecule modulators of Keap1-Nrf2-ARE pathway as potential preventive and therapeutic agents. Medicinal Research Reviews. ,vol. 32, pp. 687- 726 ,(2012) , 10.1002/MED.21257
Longqin Hu, Sadagopan Magesh, Lin Chen, Lili Wang, Timothy A. Lewis, Yu Chen, Carol Khodier, Daigo Inoyama, Lesa J. Beamer, Thomas J. Emge, Jian Shen, John E. Kerrigan, Ah-Ng Tony Kong, Sivaraman Dandapani, Michelle Palmer, Stuart L. Schreiber, Benito Munoz, Discovery of a small-molecule inhibitor and cellular probe of Keap1-Nrf2 protein-protein interaction. Bioorganic & Medicinal Chemistry Letters. ,vol. 23, pp. 3039- 3043 ,(2013) , 10.1016/J.BMCL.2013.03.013
Ryuhei Hayashi, Noriko Himori, Keiko Taguchi, Yuki Ishikawa, Kohji Uesugi, Miyuki Ito, Thomas Duncan, Motokazu Tsujikawa, Toru Nakazawa, Masayuki Yamamoto, Kohji Nishida, The role of the Nrf2-mediated defense system in corneal epithelial wound healing. Free Radical Biology and Medicine. ,vol. 61, pp. 333- 342 ,(2013) , 10.1016/J.FREERADBIOMED.2013.04.008
Melanie P. Chin, Scott A. Reisman, George L. Bakris, Megan O'Grady, Peter G. Linde, Peter A. McCullough, David Packham, Nosratola D. Vaziri, Keith W. Ward, David G. Warnock, Colin J. Meyer, Mechanisms contributing to adverse cardiovascular events in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl. American Journal of Nephrology. ,vol. 39, pp. 499- 508 ,(2014) , 10.1159/000362906
H.-C. Huang, T. Nguyen, C. B. Pickett, Regulation of the antioxidant response element by protein kinase C-mediated phosphorylation of NF-E2-related factor 2 Proceedings of the National Academy of Sciences of the United States of America. ,vol. 97, pp. 12475- 12480 ,(2000) , 10.1073/PNAS.220418997
Tao Jiang, Fei Tian, Hongting Zheng, Samantha A. Whitman, Yifeng Lin, Zhigang Zhang, Nong Zhang, Donna D. Zhang, Nrf2 suppresses lupus nephritis through inhibition of oxidative injury and the NF-κB-mediated inflammatory response Kidney International. ,vol. 85, pp. 333- 343 ,(2014) , 10.1038/KI.2013.343
Daigo Inoyama, Yu Chen, Xinyi Huang, Lesa J. Beamer, Ah-Ng Tony Kong, Longqin Hu, Optimization of fluorescently labeled Nrf2 peptide probes and the development of a fluorescence polarization assay for the discovery of inhibitors of Keap1-Nrf2 interaction. Journal of Biomolecular Screening. ,vol. 17, pp. 435- 447 ,(2012) , 10.1177/1087057111430124
Stacey Ruiz, Pablo E. Pergola, Richard A. Zager, Nosratola D. Vaziri, Targeting the transcription factor Nrf2 to ameliorate oxidative stress and inflammation in chronic kidney disease. Kidney International. ,vol. 83, pp. 1029- 1041 ,(2013) , 10.1038/KI.2012.439
Pei-Yi Tsai, Shuk-Man Ka, Jia-Ming Chang, Hsiang-Cheng Chen, Hao-Ai Shui, Chen-Yun Li, Kuo-Feng Hua, Wen-Liang Chang, Jiann-Jyh Huang, Sung-Sen Yang, Ann Chen, Epigallocatechin-3-gallate prevents lupus nephritis development in mice via enhancing the Nrf2 antioxidant pathway and inhibiting NLRP3 inflammasome activation Free Radical Biology and Medicine. ,vol. 51, pp. 744- 754 ,(2011) , 10.1016/J.FREERADBIOMED.2011.05.016
Qing Qing Wu, Yanxia Wang, Martin Senitko, Colin Meyer, W. Christian Wigley, Deborah A. Ferguson, Eric Grossman, Jianlin Chen, Xin J. Zhou, John Hartono, Pamela Winterberg, Bo Chen, Anapam Agarwal, Christopher Y. Lu, Bardoxolone methyl (BARD) ameliorates ischemic AKI and increases expression of protective genes Nrf2, PPARγ, and HO-1 American Journal of Physiology-renal Physiology. ,vol. 300, pp. 1180- 1192 ,(2011) , 10.1152/AJPRENAL.00353.2010