Unilateral Ureteral Obstruction Evokes Renal Tubular Apoptosis Via the Enhanced Oxidative Stress and Endoplasmic Reticulum Stress in the Rat
Resource
NEUROUROLOGY AND URODYNAMICS v.30 n.3 pp.472-479
Journal
Neurourology and Urodynamics
Pages
472-479
Date Issued
2011
Date
2011
Author(s)
YEH, CHUNG-SHINN
CHIANG, HAN-SUN
LAI, TING-YU
CHIEN, CHIANG-TING
Abstract
Purpose: Oxidative stress and endoplasmic reticulum ER stress may induce renal apoptosis and contribute to the pathogenesis of the kidney with unilateral ureteral obstruction UUO. Materials and Methods: We induced UUO the female Wistar rats by ligation of the left ureter at the ureteropelvic junction. TheUUOkidney 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 andapoptosis-related proteins expression intheUUOkidney. Results: WefoundthatUUOdecreasedrenal bloodflowand increased renal vascular resistance and renal ROS. UUOdecreased renal manganese superoxide dismutaseMnSOD and catalase protein expression in a time-dependent manner. Increased-4-HNEstain 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 likeERstress-response protein 25 and glucose- regulated protein 78 and ER- associated apoptosis proteins, c -JUN NH2-terminal kinase, and caspase 12, in the kidney. Subsequently, UUOenhanced 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.
Subjects
apoptosis
endoplasmic reticulum stress
kidney
oxidative stress
unilateral ureteral obstruction