Novel xanthine oxidase-based cell model using HK-2 cell for screening antihyperuricemic functional compounds

Area of Science:

• Biochemistry
• Metabolic Diseases
• Nephrology

Background:

• Hyperuricemia, a metabolic disorder from purine metabolism dysfunction, is increasingly prevalent globally.
• Understanding the molecular basis of hyperuricemia is crucial for developing effective treatments.

Purpose of the Study:

• To establish and validate an in vitro cell model for high uric acid production using human kidney cells (HK-2).
• To analyze the molecular mechanisms underlying hyperuricemia in this cell model.
• To assess the utility of the model for screening potential antihyperuricemic compounds.

Main Methods:

• Cultured human kidney (HK-2) cells were used to create a hyperuricemia model.
• Adenosine was added to induce uric acid precursor production (inosine, hypoxanthine).
• High-performance liquid chromatography (HPLC) and RNA-Seq (transcriptome analysis) were employed for metabolite and gene expression profiling.

Main Results:

• Adenosine successfully induced uric acid precursor synthesis in HK-2 cells.
• The model's validity was confirmed by the significant reduction of uric acid production by known antihyperuricemic drugs (allopurinol, probenecid, febuxostat) and bioactive compounds (glutathione, tryptophan, carnosine).
• RNA-Seq analysis revealed the model's potential to mimic in vivo cell growth patterns.

Conclusions:

• The established HK-2 cell model provides a rapid and valid platform for in vitro screening of antihyperuricemic agents.
• This model aids in understanding hyperuricemia's molecular basis and evaluating potential therapeutic compounds.