ArticleInternational urology and nephrology2016
Activation of general control nonderepressible 2 kinase protects human glomerular endothelial cells from harmful high-glucose-induced molecular pathways.
Article in International urology and nephrology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 20 citations in OpenAlex.
- Alkylating Agent-Induced FANCL Impairment Damages Pulmonary Arterial, Venous, and Microvascular Endothelial Cells and Predisposes to PAH/PVOD.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- The status of studies on the mechanism of microcirculatory dysfunction in the process of diabetic kidney injury.Diabetology & metabolic syndrome · 2025Review
- Protein kinase C and endothelial dysfunction in select vascular diseases.Frontiers in cardiovascular medicine · 2025Review
- Multiple Roles of the Stress Sensor GCN2 in Immune Cells.International journal of molecular sciences · 2023Review
- A unifying model of glucotoxicity in human renal proximal tubular epithelial cells and the effect of the SGLT2 inhibitor dapagliflozin.International urology and nephrology · 2020Article
- Ameliorative Effects of Bredemolic Acid on Markers Associated with Renal Dysfunction in a Diet-Induced Prediabetic Rat Model.Oxidative medicine and cellular longevity · 2020Article
- Article
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- Allopurinol protects human glomerular endothelial cells from high glucose-induced reactive oxygen species generation, p53 overexpression and endothelial dysfunction.International urology and nephrology · 2018Article
- Indoleamine 2, 3-dioxygenase (IDO) increases during renal fibrogenesis and its inhibition potentiates TGF-β 1-induced epithelial to mesenchymal transition.BMC nephrology · 2017Article
- The kynurenine:tryptophan ratio as a predictor of incident type 2 diabetes mellitus in individuals with coronary artery disease.Diabetologia · 2017Article
- Zinc Finger E-Box Binding Protein 2 (ZEB2) Suppress Apoptosis of Vascular Endothelial Cells Induced by High Glucose Through Mitogen-Activated Protein Kinases (MAPK) Pathway Activation.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Tryptophan depletion under conditions that imitate insulin resistance enhances fatty acid oxidation and induces endothelial dysfunction through reactive oxygen species-dependent and independent pathways.Molecular and cellular biochemistry · 2017Article
- Klotho attenuates diabetic nephropathy in db/db mice and ameliorates high glucose-induced injury of human renal glomerular endothelial cells.Cell cycle (Georgetown, Tex.)Article
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6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeConsidering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC).
methodsGEnC were cultured under normal or high-glucose conditions in the presence or not of the GCN2 kinase activator, tryptophanol. Glucose transporter 1 (GLUT1) expression was assessed by western blotting and reactive oxygen species (ROS) using a fluorogenic probe. Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting.
resultsHigh glucose induced GLUT1 expression, increased ROS and inhibited GAPDH. Also it increased the polyol pathway product sorbitol, PKC activity, the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway and the advanced glycation endproducts' precursor methylglyoxal. Co-treatment of GEnC with tryptophanol restored the above high-glucose-induced alterations.
conclusionsActivation of GCN2 kinase protects GEnC from high-glucose-induced harmful molecular pathways. By inhibiting concurrently many pathways involved in DN pathogenesis, GCN2 kinase may serve as a pharmaceutical target for the treatment of DN.
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