title: Role of reactive oxygen species-mediated endoplasmic reticulum stress in contrast-induced renal tubular cell apoptosis.
abstract: BACKGROUND
  Renal tubular cell apoptosis is a key mechanism of contrast-induced acute kidney injury. It has been reported that endoplasmic reticulum (ER) stress is the underlying mechanism of high osmolar contrast-induced renal tubular cell apoptosis. Whether ER stress is involved in low osmolar contrast-induced renal tubular cell injury remains unclear. In the present study, the roles of ER stress in iopromide-induced (a low osmolar contrast) renal tubular cell apoptosis and the effects of N-acetylcysteine (NAC) on ER stress were investigated.
  
  
  METHODS
  NRK-52E cells were exposed to different concentrations of iopromide [50, 100 and 150 mg iodine (I)/ml] for 4 h. In a separate experiment, NRK-52E cells were exposed to iopromide (100 mg I/ml, 4 h) with or without NAC (10 mmol/l). NAC was added 1 h before incubation with iopromide. Apoptosis was determined by Hoechst staining and flow cytometry. The intracellular formation of reactive oxygen species (ROS) was detected by confocal microscopy with fluorescent probe CM-H2DCFDA. The expression of glucose-regulated protein 78 (GRP78) and CAAT/enhancer-binding protein homologous protein (CHOP) was determined by Western blot.
  
  
  RESULTS
  Iopromide induced NRK-52E cell apoptosis in a concentration-dependent manner. The intracellular ROS production increased significantly following iopromide exposure in the NRK-52E cells. Significantly increased expressions of GRP78 and CHOP were observed in the NRK-52E cells exposed to iopromide for 4 h; NAC attenuated iopromide-induced NRK-52E cell apoptosis by inhibiting the overproduction of intracellular ROS and subsequently suppressing the overexpression of GRP78 and CHOP.
  
  
  CONCLUSIONS
  ROS-mediated ER stress is involved in contrast-induced renal tubular cell apoptosis.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Yang
authors.forename: Dingwei
authors.initials: D
authors.lastname: Yang
authors.forename: Dingping
authors.initials: D
authors.lastname: Yang
authors.forename: Ruhan
authors.initials: R
authors.lastname: Jia
authors.forename: Guohua
authors.initials: G
authors.lastname: Ding
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured; D003287:Contrast Media / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000378:metabolism; D007472:Iohexol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D023421:Models, Animal; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D000111:Acetylcysteine; D003287:Contrast Media; D016166:Free Radical Scavengers; D006360:Heat-Shock Proteins; D007472:Iohexol; D017382:Reactive Oxygen Species; D051742:Transcription Factor CHOP; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C038192:iopromide