Targeting Nrf2 by dihydro‐CDDO‐trifluoroethyl amide enhances autophagic clearance and viability of β‐cells in a setting of oxidative stress. Issue 12 (8th May 2014)

• Record Type: Journal Article
• Authors: Li, Wenjuan; Wu, Weiwei; Song, Haibo; Wang, Fang; Li, Huanjie; Chen, Li; Lai, Yimu; Janicki, Joseph S.; Ward, Keith W.; Meyer, Colin J.; Wang, Xing Li; Tang, Dongqi; Cui, Taixing
• Is Part Of: FEBS letters. Volume 588:Issue 12(2014)
• Page Start: 2115
• Page End: 2124
• Publication Date: 2014-05-08
• Subjects: Nrf2 -- β-Cells -- Oxidative stress -- Ubiquitination -- Autophagy -- Diabetes; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.04.046
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Nrf2 appears to be a critical regulator of diabetes in rodents. However, the underlying mechanisms as well as the clinical relevance of the Nrf2 signaling in human diabetes remain to be fully understood. Herein, we report that islet expression of Nrf2 is upregulated at an earlier stage of diabetes in both human and mice. Activation of Nrf2 suppresses oxidative stress and oxidative stress‐induced β‐cell apoptosis while enhancing autophagic clearance in isolated rat islets. Additionally, oxidative stress per se activated autophagy in β‐cells. Thus, these results reveal that Nrf2 drives a novel antioxidant independent autophagic clearance for β‐cell protection in the setting of diabetes. Abstract : Nrf2 is upregulated in islets at early stage of diabetes in human. Activation of Nrf2 by dh404 suppresses oxidative stress and prevents oxidative stress‐induced β‐cell apoptosis. Activation of Nrf2 by dh404 enhances oxidative stress‐induced autophagic clearance of ubiquitinated proteins in islets.