title: Involvement of NOX in the regulation of renal tubular expression of Na/K-ATPase in acute unilateral ureteral obstruction rats.
abstract: OBJECTIVE
  Renal tubular expression of Na/K-ATPase has been reported to be rapidly reduced in kidneys after unilateral ureteral obstruction (UUO), contributing to compromised sodium regulation. In this study, apocynin was utilized to test the hypothesis that the renal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) system is involved in the regulation of Na/K-ATPase expression in early UUO.
  
  
  METHODS
  Eighty Wistar rats underwent UUO or sham surgery, and half of each group was administered 100 mg/kg apocynin by oral gavage after surgery. Renal tissue samples were collected on day 1 and day 3 after surgery and the distribution of NOX2, NOX4 and Na/K-ATPase was assessed by immunofluorescence and immunohistochemical staining. The Heme oxygenase-1 (HO-1), NOX2, NOX4, osteopontin, Na/K-ATPase and aquaporin-1 (AQP-1) content of renal homogenates was assessed by immunoblotting, and malondialdehyde (MDA), nitric oxide (NO) content was assessed by biochemical analyses. Activity of inducible NO synthase (iNOS) and antioxidant enzymes was assessed by enzymatic assay.
  
  
  RESULTS
  Kidney Na/K-ATPase and AQP-1 content was decreased, and MDA and NOX4, NOX2 and HO-1 content were increased in the obstructed kidneys of UUO rats. Apocynin attenuated these changes and partially, but significantly, reversed the downregulation of Na/K-ATPase and AQP-1 in UUO rats. However, apocynin did not alter iNOS activity and NO production, osteopontin expression or the activity of antioxidant enzymes.
  
  
  CONCLUSIONS
  Activation of the NOX system and subsequent production of ROS are likely responsible for the downregulation of renal tubular Na/K-ATPase expression in early UUO.
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital and Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, China.
authors.forename: Changxuan
authors.initials: C
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Song
authors.forename: Lei
authors.initials: L
authors.lastname: Qu
authors.forename: Jiawei
authors.initials: J
authors.lastname: Tang
authors.forename: Liqiang
authors.initials: L
authors.lastname: Meng
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000098:Acetophenones / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007684:Kidney Tubules / Q000201:enzymology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D053495:Osteopontin / Q000096:biosynthesis / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis*; D014517:Ureteral Obstruction / Q000188:drug therapy / Q000201:enzymology*
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D053495:Osteopontin; D009569:Nitric Oxide; C056165:acetovanillone; D019255:NADPH Oxidases; D000254:Sodium-Potassium-Exchanging ATPase