ArticleAntioxidants & redox signaling2015
Targeting of Gamma-Glutamyl-Cysteine Ligase by miR-433 Reduces Glutathione Biosynthesis and Promotes TGF-β-Dependent Fibrogenesis.
Article in Antioxidants & redox signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Natural Compounds and Glutathione: Beyond Mere Antioxidants.Antioxidants (Basel, Switzerland) · 2023Review
- Altered MicroRNA Maturation in Ischemic Hearts: Implication of Hypoxia on XPO5 and DICER1 Dysregulation and RedoximiR State.Antioxidants (Basel, Switzerland) · 2023Article
- The Biochemistry and Effectiveness of Antioxidants in Food, Fruits, and Marine Algae.Antioxidants (Basel, Switzerland) · 2023Review
- Hormesis and Oxidative Distress: Pathophysiology of Reactive Oxygen Species and the Open Question of Antioxidant Modulation and Supplementation.Antioxidants (Basel, Switzerland) · 2022Review
- H3K4 di-methylation governs smooth muscle lineage identity and promotes vascular homeostasis by restraining plasticity.Developmental cell · 2021Article
- Understanding the Relationship between Glutathione, TGF-β, and Vitamin D in CombatingJournal of clinical medicine · 2020Review
- Endoplasmic reticulum stress and glutathione therapeutics in chronic lung diseases.Redox biology · 2020Review
- Targeting the progression of chronic kidney disease.Nature reviews. Nephrology · 2020Review
- MicroRNA-221 is a potential biomarker of myocardial hypertrophy and fibrosis in hypertrophic obstructive cardiomyopathy.Bioscience reports · 2020Article
- miRNA Regulation of Glutathione Homeostasis in Cancer Initiation, Progression and Therapy Resistance.MicroRNA (Shariqah, United Arab Emirates) · 2020Review
- Article
- MicroRNA Networks Modulate Oxidative Stress in Cancer.International journal of molecular sciences · 2019Review
- Review
- The Precursor to Glutathione (GSH), γ-Glutamylcysteine (GGC), Can Ameliorate Oxidative Damage and Neuroinflammation Induced by AβFrontiers in aging neuroscience · 2019Article
- Effects of Brain-Derived Neurotrophic Factor on MicroRNA Expression Profile in Human Endothelial Progenitor Cells.Cell transplantation · 2018Article
- MicroRNAs as Potential Regulators of Glutathione Peroxidases Expression and Their Role in Obesity and Related Pathologies.International journal of molecular sciences · 2018Review
- Role of glutathione biosynthesis in endothelial dysfunction and fibrosis.Redox biology · 2018Article
- European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS).Redox biology · 2017Review
- Cardiac fibrosis and miR-433.Annals of translational medicine · 2016Article
- MicroRNA-mediated regulation of glutathione and methionine metabolism and its relevance for liver disease.Free radical biology & medicine · 2016Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsGlutathione (GSH) is the main antioxidant against cell damage. Several pathological states course with reduced nucleophilic tone and perturbation of redox homeostasis due to changes in the 2GSH/GSSG ratio. Here, we investigated the regulation of the rate-limiting GSH biosynthetic heterodimeric enzyme γ-glutamyl-cysteine ligase (GCL) by microRNAs (miRNAs).
results"In silico" analysis of the 3'- untranslated regions (UTRs) of both catalytic (GCLc) and regulatory (GCLm) subunits of GCL enabled an identification of miR-433 as a strong candidate for the targeting of GCL. Transitory overexpression of miR-433 in human umbilical vein endothelial cells (HUVEC) showed a downregulation of both GCLc and GCLm in a nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-independent manner. Increases in pro-oxidant stimuli such as exposure to hydrogen peroxide or GSH depletion in endothelial and hepatic cells caused an expected increase in GCLc and GCLm protein expression and abrogation of miR-433 levels, thus supporting a cross-regulation of these pathways. Treatment of HUVEC with miR-433 resulted in reduced antioxidant and redox potentials, increased S-glutathionylation, and reduced endothelial nitric oxide synthase activation. In vivo models of renal and hepatic fibrosis were associated with transforming growth factor β1 (TGF-β1)-related reduction of GCLc and GCLm levels that were miR-433 dependent. INNOVATION AND
conclusionWe describe for the first time an miRNA, miR-433, capable of directly targeting GCL and promoting functional consequences in endothelial physiology and fibrotic processes by decreasing GSH levels.
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