title: Unilateral ureteral obstruction evokes renal tubular apoptosis via the enhanced oxidative stress and endoplasmic reticulum stress in the rat.
abstract: OBJECTIVE
  Oxidative stress and endoplasmic reticulum (ER) stress may induce renal apoptosis and contribute to the pathogenesis of the kidney with unilateral ureteral obstruction (UUO).
  
  
  METHODS
  We induced UUO the female Wistar rats by ligation of the left ureter at the ureteropelvic junction. The UUO kidney was performed from 4 hr to 7 days course. At the indicated time, we measured the arterial blood pressure and renal blood flow in each rat, renal ROS measurement in vivo by a chemiluminescence analyzer. We performed immunohistochemistry of monocyte/macrophage (ED-1) stain for leukocyte infiltration, 4-hydroxynoneal (4-HNE) stain for ROS products, and apoptosis by terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) and Western blot to analyze ER stress-associated and apoptosis-related proteins expression in the UUO kidney.
  
  
  RESULTS
  We found that UUO decreased renal blood flow and increased renal vascular resistance and renal ROS. UUO decreased renal manganese superoxide dismutase (MnSOD) and catalase protein expression in a time-dependent manner. Increased 4-HNE stain in the renal tubules and ED-1 stain in the renal tubulointerstitial compartment occurred after 4 hr of UUO in the kidney. UUO significantly enhanced ER stress markers like ER stress-response protein 25 and glucose-regulated protein 78 and ER-associated apoptosis proteins, c-JUN NH(2) -terminal kinase, and caspase 12, in the kidney. Subsequently, UUO enhanced renal pro-apoptotic Bax and caspase 3 expression and decreased anti-apoptotic Bcl-2 expression, leading to renal tubular apoptosis.
  
  
  CONCLUSIONS
  Our data suggest that renal tubular apoptosis induced by oxidative stress and ER stress occurred in the UUO kidney.
authors.affiliation: Division of Urology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors.forename: Chung-Hsin
authors.initials: CH
authors.lastname: Yeh
authors.forename: Han-Sun
authors.initials: HS
authors.lastname: Chiang
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Lai
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chien
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001794:Blood Pressure; D053454:Caspase 12 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007684:Kidney Tubules / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D007962:Leukocytes / Q000378:metabolism; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014517:Ureteral Obstruction / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D014655:Vascular Resistance; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D000447:Aldehydes; D053454:Caspase 12; D053148:Caspase 3; D002374:Catalase; D006360:Heat-Shock Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D013482:Superoxide Dismutase; D051028:bcl-2-Associated X Protein; C494828:Bax protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C506443:Casp12 protein, rat; C505410:Casp3 protein, rat; C027576:4-hydroxy-2-nonenal