title: Decreased renal organic anion transporter 3 expression in type 1 diabetic rats.
abstract: BACKGROUND
  Organic anion transporter 3 (Oat3) plays an essential role in the renal excretion of organic anions. Reduced renal Oat3 expression potentially contributes to an impaired anion clearance and causes abnormal kidney function. This study examined the effects of diabetes on the expression and function of rat renal Oat3.
  
  
  METHODS
  Experimental diabetes was induced by the administration of streptozotocin. Diabetic rats were randomly assigned to the treatment group or no treatment group with insulin for 4 weeks. The expression of renal Oat3, protein kinase Cα (PKCα), phospho-PKCα and nuclear factor kappa B (NF-κB) p65 were determined by immunoblotting. Estrone sulfate (ES) uptake into renal cortical slices was used as an indicator of renal Oat3 function.
  
  
  RESULTS
  The reduced expression of renal Oat3 was related to the decrease in [H]ES uptake in a renal cortical slice of the diabetic rat. Insulin treatment restored the impairment of renal Oat3 function and expression. These may be because of the hyperglycemia-induced oxidative stress effectively activating the PKCα and NF-κB. Insulin treatment abolished these processes.
  
  
  CONCLUSIONS
  These data are the first to show that the decreased function and expression of renal Oat3 in diabetes was associated with an increase in reactive oxygen species production coinciding with the activation of PKC and NF-κB signaling pathway. These events may affect the transporter protein translocation and/or expression.
authors.affiliation: Department of Physiology (PA, CS, AL), Faculty of Medicine, Chiang Mai University, Chiang Mai; and Department of Physiology (VC), Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Arjinajarn
authors.initials: A
authors.lastname: Phatchawan
authors.forename: Srimaroeng
authors.initials: S
authors.lastname: Chutima
authors.forename: Chatsudthipong
authors.initials: C
authors.lastname: Varanuj
authors.forename: Lungkaphin
authors.initials: L
authors.lastname: Anusorn
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004970:Estrone / Q000031:analogs & derivatives / Q000494:pharmacology; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D029362:Organic Anion Transporters, Sodium-Independent; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D014280:Triglycerides; C114338:organic anion transport protein 3; D004970:Estrone; D008315:Malondialdehyde; D051571:Protein Kinase C-alpha; D013755:Tetradecanoylphorbol Acetate; C017296:estrone sulfate