ArticlePloS one2015
The effect of Nrf2 pathway activation on human pancreatic islet cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Putative molecular targets for vitamin A in neutralizing oxidative stress in acute and chronic pancreatitis - a systematic review.Naunyn-Schmiedeberg's archives of pharmacology · 2023Pooled it
- Review
- Bardoxolone Methyl Ameliorates Chemotherapy-Induced Neuropathic Pain by Activation of Phosphorylated Nuclear Factor Erythroid 2-Related Factor 2 in the Dorsal Root Ganglia.Anesthesia and analgesia · 2024Article
- Cytoprotective Effect of Pteryxin on Insulinoma MIN6 Cells Due to Antioxidant Enzymes Expression via Nrf2/ARE Activation.Antioxidants (Basel, Switzerland) · 2023Article
- Nrf2 and Antioxidant Response in Animal Models of Type 2 Diabetes.International journal of molecular sciences · 2023Review
- Crosstalk between G-quadruplex and ROS.Cell death & disease · 2023Review
- Anti-Oxidative Therapy in Islet Cell Transplantation.Antioxidants (Basel, Switzerland) · 2022Review
- Nrf2 Regulates β-Cell Mass by Suppressing β-Cell Death and Promoting β-Cell Proliferation.Diabetes · 2022Article
- Dysregulation of β-Cell Proliferation in Diabetes: Possibilities of Combination Therapy in the Development of a Comprehensive Treatment.Biomedicines · 2022Review
- Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells.Frontiers in endocrinology · 2022Review
- Antioxidant Therapy in Pancreatitis.Antioxidants (Basel, Switzerland) · 2021Review
- Melatonin Modulates the Antioxidant Defenses and the Expression of Proinflammatory Mediators in Pancreatic Stellate Cells Subjected to Hypoxia.Antioxidants (Basel, Switzerland) · 2021Article
- Current Pharmacological Intervention and Medical Management for Diabetic Kidney Transplant Recipients.Pharmaceutics · 2021Review
- The Role of Oxidative Stress in Pancreatic β Cell Dysfunction in Diabetes.International journal of molecular sciences · 2021Review
- Nrf2: The Master and Captain of Beta Cell Fate.Trends in endocrinology and metabolism: TEM · 2021Review
- Potential Benefits of Nrf2/Keap1 Targeting in Pancreatic Islet Cell Transplantation.Antioxidants (Basel, Switzerland) · 2020Review
- A State-of-the-Science Review of Arsenic's Effects on Glucose Homeostasis in Experimental Models.Environmental health perspectives · 2020Review
- Activation of NF-E2 p45-related factor-2 transcription and inhibition of intestinal tumor development by AHCC, a standardized extract of culturedJournal of clinical biochemistry and nutrition · 2019Article
- Human mesenchymal stem cells improve rat islet functionality under cytokine stress with combined upregulation of heme oxygenase-1 and ferritin.Stem cell research & therapy · 2019Article
- CD28 Deficiency Ameliorates Thoracic Blast Exposure-Induced Oxidative Stress and Apoptosis in the Brain through the PI3K/Nrf2/Keap1 Signaling Pathway.Oxidative medicine and cellular longevity · 2019Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPancreatic islets are known to contain low level of antioxidants that renders them vulnerable to oxidative stress. Nrf2 is the master regulator of numerous genes, encoding antioxidant, detoxifying, and cytoprotective molecules. Activation of Nrf2 pathway induces up-regulation of numerous genes encoding antioxidant and phase II detoxifying enzymes and related proteins. However, little is known regarding the role of this pathway in human islet cells. The aim was to investigate the effect of Nrf2 activator (dh404, CDDO-9,11-dihydro-trifluoroethyl amide) on human islet cells.
methodsHuman islets were obtained from cadaveric donors. After dh404 treatment, Nrf2 translocation, mRNA expression, and protein abundance of its key target gene products were examined. The proportion of dh404-treated or non-treated viable islet beta cells was analyzed using flowcytemetry. The cytoprotective effects against oxidative stress and production of inflammatory mediators, and in vivo islet function after transplantation were determined.
resultsNrf2 nuclear translocation was confirmed by con-focal microscope within 2 hours after treatment, which was associated with a dose-dependent increase in mRNA expression of anti-oxidants, including NQO1, HO-1, and GCLC. Enhanced HO-1 expression in dh404 treated islets was confirmed by Western Blot assay. Islet function after transplantation (2000 IEQ/mouse) to diabetic nude mice was not affected with or without dh404 treatment. After induction of oxidative stress with hydrogen peroxide (200 μM) the proportion of dh404-treated viable islet cells was significantly higher in the dh404-treated than untreated islets (74% vs.57%; P<0.05). Dh404 significantly decreased production of cytokines/chemokines including IL-1β, IL-6, IFN-γ and MCP-1.
conclusionTreatment of human pancreatic islets with the potent synthetic Nrf2 activator, dh404, significantly increased expression of the key anti-oxidants enzymes, decreased inflammatory mediators in islets and conferred protection against oxidative stress in beta cells.
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