dc.creator | Eleftheriadis T., Pissas G., Antoniadi G., Liakopoulos V., Stefanidis I. | en |
dc.date.accessioned | 2023-01-31T07:37:13Z | |
dc.date.available | 2023-01-31T07:37:13Z | |
dc.date.issued | 2018 | |
dc.identifier | 10.1007/s11255-017-1733-5 | |
dc.identifier.issn | 03011623 | |
dc.identifier.uri | http://hdl.handle.net/11615/71317 | |
dc.description.abstract | Purpose: Mitochondrial reactive oxygen species (ROS) overproduction in capillary endothelial cells is a prerequisite for the development of diabetic nephropathy. Inhibition of xanthine oxidase, another ROS generator, ameliorates experimental diabetic nephropathy. To test the hypothesis that the initial high glucose-induced ROS production by the mitochondria activates xanthine oxidase, which afterward remains as the major source of ROS, we cultured primary human glomerular endothelial cells (GEnC) under normal or high-glucose conditions, with or without the xanthine oxidase inhibitor allopurinol. Methods: ROS generation and nitric oxide synthase (NOS) activity were assessed by chemiluminescence or colorimetrically. Levels of intercellular adhesion molecule 1 (ICAM-1), p53 and phosphorylated p53 (p-p53) were assessed by western blotting. Results: Allopurinol prevented high glucose-induced ROS generation indicating that xanthine oxidase is the major source of ROS. Allopurinol protected GEnC from endothelial dysfunction since it prevented the high glucose-induced decrease in NOS activity and increase in ICAM-1 expression. Allopurinol reduced p53 and p-p53 levels induced by high glucose suggesting an axis of xanthine oxidase-derived ROS, DNA damage, p53 stabilization and endothelial dysfunction that may contribute to the pathogenesis of diabetic nephropathy. Conclusions: Allopurinol protects GEnC from high glucose-induced ROS generation, p53 overexpression and endothelial dysfunction. These data provide a pathogenetic mechanism that supports the results of experimental and clinical studies about the beneficial effect of xanthine oxidase inhibitors on the development of diabetic nephropathy. © 2017, Springer Science+Business Media B.V. | en |
dc.language.iso | en | en |
dc.source | International Urology and Nephrology | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85032833993&doi=10.1007%2fs11255-017-1733-5&partnerID=40&md5=183d9db435a6bf7d59116f0cefca5757 | |
dc.subject | allopurinol | en |
dc.subject | glucose | en |
dc.subject | intercellular adhesion molecule 1 | en |
dc.subject | nitric oxide synthase | en |
dc.subject | protein p53 | en |
dc.subject | reactive oxygen metabolite | en |
dc.subject | allopurinol | en |
dc.subject | glucose | en |
dc.subject | ICAM1 protein, human | en |
dc.subject | intercellular adhesion molecule 1 | en |
dc.subject | nitric oxide synthase | en |
dc.subject | protein p53 | en |
dc.subject | reactive oxygen metabolite | en |
dc.subject | scavenger | en |
dc.subject | Article | en |
dc.subject | cell protection | en |
dc.subject | controlled study | en |
dc.subject | cytotoxicity | en |
dc.subject | DNA damage | en |
dc.subject | endothelial dysfunction | en |
dc.subject | endothelium cell | en |
dc.subject | enzyme activity | en |
dc.subject | human | en |
dc.subject | human cell | en |
dc.subject | kidney cell | en |
dc.subject | oxidative stress | en |
dc.subject | protein expression | en |
dc.subject | protein phosphorylation | en |
dc.subject | protein stability | en |
dc.subject | upregulation | en |
dc.subject | cell culture | en |
dc.subject | cell survival | en |
dc.subject | cytology | en |
dc.subject | drug effect | en |
dc.subject | endothelium cell | en |
dc.subject | glomerulus | en |
dc.subject | metabolism | en |
dc.subject | physiology | en |
dc.subject | primary cell culture | en |
dc.subject | Allopurinol | en |
dc.subject | Cell Survival | en |
dc.subject | Cells, Cultured | en |
dc.subject | Endothelial Cells | en |
dc.subject | Free Radical Scavengers | en |
dc.subject | Glucose | en |
dc.subject | Humans | en |
dc.subject | Intercellular Adhesion Molecule-1 | en |
dc.subject | Kidney Glomerulus | en |
dc.subject | Nitric Oxide Synthase | en |
dc.subject | Primary Cell Culture | en |
dc.subject | Reactive Oxygen Species | en |
dc.subject | Tumor Suppressor Protein p53 | en |
dc.subject | Springer Netherlands | en |
dc.title | Allopurinol protects human glomerular endothelial cells from high glucose-induced reactive oxygen species generation, p53 overexpression and endothelial dysfunction | en |
dc.type | journalArticle | en |