Hypoxia preconditioning attenuates bladder overdistension-induced oxidative injury by up-regulation of Bcl-2 in the rat.
We explored whether hypoxic preconditioning minimizes oxidative injury induced by overdistension/emptying in the rat bladder. For hypoxic preconditioning, female Wistar rats were placed in a hypobaric chamber (380 Torr) 15 h day(-1) for 28 days. Overdistension was induced by infusion of two times the threshold volume of saline into the bladder and was maintained for 1 or 2 h, followed by drainage/emptying. During overdistension (ischaemia) and emptying (reperfusion) periods, a bursting increase of reactive oxygen species (ROS) from the bladder was originated from the large numbers of infiltrating leucocytes and scattered resident cells, including urothelial, submucosal, and smooth muscle cells. ROS impaired the voiding function by a reduction of bladder afferent and efferent nerve activity and bethanecol- or ATP-induced detrusor contraction. ROS enhanced pro-apoptotic mechanisms, including increases in the Bax/Bcl-2 ratio, CPP32 expression, and poly(ADP-ribose) polymerase (PARP) fragments with subsequent apoptotic cell formation in the insulted bladders. Hypoxia preconditioning up-regulated Bcl-2 expression in the bladder and significantly reduced the levels of ROS and apoptosis detected in the overdistension/emptying bladders and preserved partial voiding function. Bcl-2 up-regulation by hypoxia preconditioning contributes protection against overdistension/emptying-induced oxidative stress and injury in the bladder.
Yu
Hong-Jeng
HJ
Department of Medical Research, National Taiwan University Hospital, No. 7 Chung-Shan S. Road, Taipei, Taiwan, ROC.
Chien
Chiang-Ting
CT
Lai
Yu-Jen
YJ
Lai
Ming-Kuen
MK
Chen
Chau-Fong
CF
Levin
Robert M
RM
Hsu
Su-Ming
SM
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004108:Dilatation, Pathologic; D004231:Diuresis; D005260:Female; D005786:Gene Expression Regulation; D006439:Hemodynamics; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000503:physiopathology; D018384:Oxidative Stress; D011312:Pressure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014018:Tissue Distribution; D015854:Up-Regulation; D001743:Urinary Bladder / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species