title: Targeting Nrf2 by dihydro-CDDO-trifluoroethyl amide enhances autophagic clearance and viability of β-cells in a setting of oxidative stress.
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.
authors.affiliation: Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, China; Department of Endocrinology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Li
authors.affiliation: Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Song
authors.affiliation: Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Huanjie
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Qilu Hospital of Shandong University, Jinan 250012, China. Electronic address: chenli3@medmail.com.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: Yimu
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Department of Endocrinology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Janicki
authors.affiliation: Department of Pharmacology, Reata Pharmaceuticals, Inc., Irving, TX 75063, USA.
authors.forename: Keith W
authors.initials: KW
authors.lastname: Ward
authors.affiliation: Department of Pharmacology, Reata Pharmaceuticals, Inc., Irving, TX 75063, USA.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Meyer
authors.affiliation: Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Xing Li
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, China; Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: Dongqi
authors.initials: D
authors.lastname: Tang
authors.affiliation: Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, China; Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208, USA. Electronic address: Taixing.Cui@uscmed.sc.edu.
authors.forename: Taixing
authors.initials: T
authors.lastname: Cui
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C547749:dh404 compound; D009828:Oleanolic Acid; D006861:Hydrogen Peroxide
keywords: Autophagy; Diabetes; Nrf2; Oxidative stress; Ubiquitination; β-Cells