Urate Oxidase Knockdown Decreases Oxidative Stress in a Murine Hepatic Cell Line

Details

• Personal Author:
  Blemings KP ; Cleveland BM ; Klandorf H ; Leonard, Stephen S.
• Description:
  Humans, birds, and some primates do not express the uric acid degrading enzyme urate oxidase (UOX) and, as a result, have plasma uric acid concentrations higher than UOX expressing animals. Although high uric acid concentrations are suggested to increase the antioxidant defense system and provide a health advantage to animals without UOX, knockout mice lacking UOX develop pathological complications including gout and kidney failure. As an alternative to the knockout model, RNA interference was used to decrease UOX expression using stable transfection in a mouse hepatic cell line (ATCC, FL83B). Urate oxidase mRNA was reduced 66% (p < 0.05) compared to wild type, as measured by real time RT-PCR. To determine if UOX knockdown resulted in enhanced protection against oxidative stress, cells were challenged with hexavalent chromium (Cr(VI)) or 3-morpholinosydnonimine hydrochloride (SIN-1). Compared to wild type, cells with UOX knockdown exhibited a 37.2 +/- 3.5% reduction (p < 0.05) in the electron spin resonance (ESR) signal after being exposed to Cr(VI) and displayed less DNA fragmentation (p < 0.05) following SIN-1 treatment. Cell viability decreased in wild type cells (p < 0.05), but not cells with UOX knockdown, after treatment with SIN-1. These results are consistent with an increased intracellular uric acid concentration and an increased defense against oxidative stress. [Description provided by NIOSH]
• Subjects:
  Animals Antioxidants Biochemistry Digestive System Energy Metabolism Laboratories Liver Occupational Health Oxidants Safety
• Keywords:
  Animal-studies Antioxidation Author Keywords: Urate Oxidase Biochemical-analysis Biological-effects Cell-biology Cell-function Cell-metabolism Cell-morphology Cellular-reactions Hepatic-microsomal-enzymes Hepatocytes Laboratory-animals Liver-cells Liver-function Liver-microsomal-metabolism Metabolism Oxidation-reduction-reactions Oxidative-metabolism Oxidative-processes Oxidative Stress RNA Interference SIN-1 Uric Acid

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• ISSN:
  1942-0900
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  93-98
• Volume:
  2
• Issue:
  2
• NIOSHTIC Number:
  nn:20035498
• Citation:
  Oxidat Med Cell Longev 2009 Apr; 2(2):93-98
• Contact Point Address:
  Kenneth P. Blemings, West Virginia University, PO Box 6108, Morgantown, West Virginia 26506
• Email:
  kbleming@wvu.edu
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Oxidative Medicine and Cellular Longevity
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:47593aa5a9f089df42eea65507506814aaad93669f53a9f45a013c4869fb9cb6392145d7a1af261702fa56af9b2088e2f5953b7f94815b283a2a72c7f15e8638
• Download URL:
  https://stacks.cdc.gov/view/cdc/187336/cdc_187336_DS1.pdf
• File Type:
  [PDF - 176.58 KB ]