title: Contributions of endoplasmic reticulum stress and reactive oxygen species to renal injury in aldosterone/salt-induced rats.
abstract: BACKGROUND
  Recent studies have suggested that aldosterone (Aldo) plays a key role in the pathogenesis of renal injury; however, the molecular mechanisms of Aldo-induced renal injury have not been characterized. This study was performed to test the hypothesis that reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress contribute to the pathogenesis of Aldo- and salt-induced renal injury.
  
  
  METHODS
  Rats were uninephrectomized and treated with one of the following for 4 weeks: (1) vehicle, (2) vehicle + NaCl, (3) Aldo + NaCl or (4) Aldo + NaCl + N-acetyl-L-cysteine (NAC). Following this treatment period, the extent of renal injury was assessed by periodic acid-Schiff staining and immunohistochemistry, and the expression levels of proteins related to ER stress, as well as p47phox and p67phox in the kidney, were measured by Western blot. Intracellular ROS generation was evaluated by 2'7'-dichlorofluorescin diacetate fluorescence and ELISA kits.
  
  
  RESULTS
  Rats that received Aldo + 1% NaCl exhibited severe renal injury. ROS levels were higher in Aldo-infused rats and were inhibited by NAC. Renal cortical protein levels of GRP78, GRP94, CHOP, ATF-4, p47phox and p67phox were significantly upregulated in rats that received Aldo + 1% NaCl. Treatment with NAC significantly ameliorated the increase in the expression of these proteins.
  
  
  CONCLUSIONS
  These data suggest that ROS and ER stress play a role in the progression of Aldo- and salt-induced renal injury.
authors.affiliation: Division of Nephrology, Huashan Hospital and Institute of Nephrology, Fudan University, Shanghai, China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000450:Aldosterone; D000818:Animals; D015153:Blotting, Western; D059865:Endoplasmic Reticulum Stress; D016166:Free Radical Scavengers / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012965:Sodium Chloride; D051742:Transcription Factor CHOP / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D000111:Acetylcysteine; D051701:Activating Transcription Factor 4; D000450:Aldosterone; D016166:Free Radical Scavengers; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D019255:NADPH Oxidases; D010750:Phosphoproteins; D018809:Proliferating Cell Nuclear Antigen; D017382:Reactive Oxygen Species; D012965:Sodium Chloride; D051742:Transcription Factor CHOP; C497110:Atf4 protein, rat; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C018551:glucose-regulated proteins; C079789:neutrophil cytosol factor 67K; C060505:neutrophil cytosolic factor 1