title: Possible involvement of intracellular angiotensin II receptor in high-glucose-induced damage in renal proximal tubular cells.
abstract: BACKGROUND
  Recent studies have identified high glucose as a potent stimulus for the intracellular synthesis of angiotensin II. However, the exact roles of angiotensin II and angiotensin II type 1 receptor blockers (ARB) in high-glucose-induced renal tubular function remain unclear.
  
  
  METHODS
  N-Acetyl-beta-glucosaminidase (NAG), angiotensin II and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations in renal proximal tubular epithelial cells (RPTECs) with or without high glucose/ARB were determined using a modified commercial procedure. The changes of p22phox and cytoplasmic inhibitory kappa B (IkB) protein levels in RPTECs were measured using Western blotting.
  
  
  RESULTS
  High-glucose treatment (4x10-2 mol/L) significantly increased NAG release, angiotensin II concentrations in cell lysates and 8-OHdG and p22phox protein levels compared with those in regular glucose medium (1.75x10(-2) mol/L). ARBs (candesartan, olmesartan or valsartan; 1x10(-9)-10(-7) mol/L) showed a significant reduction in high-glucose-induced NAG, 8-OHdG and p22phox protein levels in RPTECs. Significant decreases of cytoplasmic IkB protein levels were observed in the high-glucose-treated group in RPTECs. ARBs markedly reversed high-glucose-induced reduction of IkB protein levels in RPTECs.
  
  
  CONCLUSIONS
  ARBs reduce high-glucose-induced oxidative stress in RPTECs possibly via blockade of intracellular as well as extracellular AT1 receptor signaling, which possibly protects renal tubular cell function during diabetic nephropathy.
authors.affiliation: Division of Community Medicine, Department of Community Nursing, Kochi Medical School, Nankoku, Japan. takaot@kochi-u.ac.jp
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takao
authors.forename: Taro
authors.initials: T
authors.lastname: Horino
authors.forename: Toru
authors.initials: T
authors.lastname: Kagawa
authors.forename: Reiko
authors.initials: R
authors.lastname: Matsumoto
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Shimamura
authors.forename: Koji
authors.initials: K
authors.lastname: Ogata
authors.forename: Kousuke
authors.initials: K
authors.lastname: Inoue
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Takafumi
authors.initials: T
authors.lastname: Taguchi
authors.forename: Tatsuhito
authors.initials: T
authors.lastname: Morita
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Terada
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005947:Glucose / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011945:Receptors, Angiotensin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D048828:beta-N-Acetyl-Galactosaminidase / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D011945:Receptors, Angiotensin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D019255:NADPH Oxidases; C086986:CYBA protein, human; D048828:beta-N-Acetyl-Galactosaminidase; D003849:Deoxyguanosine; D005947:Glucose