An inhibitor of the Keap1-Nrf2 protein-protein interaction protects NCM460 colonic cells and alleviates experimental colitis

作者：Lu, Meng-Chen; Ji, Jian-Ai; Jiang, Yong-Lin; Chen, Zhi-Yun; Yuan, Zhen-Wei; You, Qi-Dong^*; Jiang, Zheng-Yu^*

来源：Scientific Reports, 2016, 6(1): 26585.

DOI：10.1038/srep26585

• INFLAMMATORY-BOWEL-DISEASE
• NF-KAPPA-B
• SODIUM-INDUCED COLITIS
• NRF2-DEFICIENT MICE
• ULCERATIVE-COLITIS
• NRF2
• RECOGNITION
• ACTIVATION
• PATHWAY
• REDOX

Ulcerative colitis (UC) is a chronic relapsing-remitting form of inflammatory bowel disease (IBD) that increases the risk of colorectal cancer, the third most common malignancy in humans. Oxidative stress is a risk factor for the development of UC. The Keap1-Nrf2-ARE pathway is one of the most important defensive mechanisms against oxidative and/or electrophilic stresses. In this study, we identified CPUY192018 as a potent small-molecule inhibitor of the Keap1-Nrf2 PPI, investigated the cyto-protective effects of CPUY192018 on the NCM460 colonic cells and evaluated whether treatment with the inhibitor of the Keap1-Nrf2 PPI exerts protection on an established experimental model of UC induced by dextran sodium sulfate (DSS). Our study clearly demonstrated that CPUY192018 had a cytoprotective effect against DSS in both NCM460 cells and mouse colon via the activation of Nrf2 signaling. These results suggested that activation of Nrf2 by directly inhibiting the Keap1-Nrf2 PPI may be beneficial as a treatment for UC.

• 出版日期2016-5-24
• 单位中国药科大学