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Background: Gout could result in irreversible bone erosion, and chondrocyte might be involved in the process. Increased soluble urate is the early stage of gout and is strongly oxidative.

Objective: To explore the effect of intracellular urate on the oxidative status of chondrocytes.

Methods: A chondrocyte model was used. Serial concentrations of exogenous urate were incubated with chondrocytes for increasing amounts of time. Reactive oxygen species (ROS), oxidant, and anti-oxidant molecules were measured with biochemical assays, rt-PCR, and western blot. A urate transport inhibitor and oxidative inhibitors were used to confirm the effect of exogenous urate.

Results: All concentrations of exogenous urate stimulated the production of ROS in a time- and concentration-dependent manner, as well as oxidant molecules, including hydrogen peroxide (H 2 O 2 ), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, nitric oxide (NO) inducible nitric oxide synthase (iNOS), and these effects, could be inhibited by oxidant inhibitors. However, anti-oxidant molecules, including acidic leucine-rich nuclear phosphoprotein-32A (ANP32A), ataxia-telangiectasia mutated (ATM), heme oxygenase-1 (HO-1), and the transcription factor nuclear factor erythroid 2 (NF-E2)-related (Nrf2), was decreased by high concentrations of exogenous urate after prolonged incubation, but not by low to medium concentrations of exogenous urate. By inhibiting soluble urate trafficking, benzbromarone significantly suppressed the effect of urate stimulus on the oxidant and anti-oxidant molecules.

Conclusion: Intracellular soluble urate could regulate chondrocyte redox balance in a time and concentration-dependent manner, and would be a target for regulating and protecting chondrocyte function in the early gout stage.

Titel:	Time- and Concentration-Dependent Stimulation of Oxidative Stress in Chondrocytes by Intracellular Soluble Urate.
Autor/in / Beteiligte Person:	Zhang, B ; Di, H ; Zhang, Y ; Han, X ; Yin, Y ; Han, Y ; Cao, Y ; Zeng, X
Zeitschrift:	Current molecular medicine, Jg. 24 (2024), Heft 2, S. 233
Veröffentlichung:	Hilversum, The Netherlands ; Boca Raton, FL : Bentham Science Publishers, c2001-, 2024
Medientyp:	academicJournal
ISSN:	1875-5666 (electronic)
DOI:	10.2174/1566524023666221227102157
Schlagwort:	Humans Reactive Oxygen Species metabolism Antioxidants pharmacology Chondrocytes metabolism Hydrogen Peroxide pharmacology Oxidative Stress Heme Oxygenase-1 metabolism Oxidants pharmacology NF-E2-Related Factor 2 metabolism Nuclear Proteins RNA-Binding Proteins Uric Acid pharmacology Gout
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Curr Mol Med] 2024; Vol. 24 (2), pp. 233-243. MeSH Terms: Uric Acid* / pharmacology ; Gout* ; Humans ; Reactive Oxygen Species / metabolism ; Antioxidants / pharmacology ; Chondrocytes / metabolism ; Hydrogen Peroxide / pharmacology ; Oxidative Stress ; Heme Oxygenase-1 / metabolism ; Oxidants / pharmacology ; NF-E2-Related Factor 2 / metabolism ; Nuclear Proteins ; RNA-Binding Proteins Grant Information: 3332020013 Fundamental Research Funds for the Central Universities; 81901667, 82071841 National Natural Science Foundation of China Contributed Indexing: Keywords: Chondrocyte; bone remodeling.; oxidative stress; reactive oxygen species; redox balance; urate Substance Nomenclature: 0 (Reactive Oxygen Species) ; 268B43MJ25 (Uric Acid) ; 0 (Antioxidants) ; BBX060AN9V (Hydrogen Peroxide) ; EC 1.14.14.18 (Heme Oxygenase-1) ; 0 (Oxidants) ; 0 (NF-E2-Related Factor 2) ; 0 (ANP32A protein, human) ; 0 (Nuclear Proteins) ; 0 (RNA-Binding Proteins) Entry Date(s): Date Created: 20221229 Date Completed: 20240115 Latest Revision: 20240529 Update Code: 20240530

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Time- and Concentration-Dependent Stimulation of Oxidative Stress in Chondrocytes by Intracellular Soluble Urate.