NAD(P)H:quinone oxidoreductase 1 protects bladder epithelium against painful bladder syndrome in mice

Painful bladder syndrome (PBS), or interstitial cystitis, is a poorly understood chronic disease that is characterized by thinning of the bladder epithelium and intense pain. Here we demonstrate that NAD(P)H:quinone oxidoreductase 1(-/-) (NQO1(-/-)) mice developed in our laboratory represent a new animal model of PBS. NQO1 is known to protect against physiological stress as well as protecting transcription factors against proteasomal degradation. In this study we demonstrate that NQO1 is necessary for bladder epithelium integrity and to prevent the development/progression of PBS. We observed downregulation of energy metabolism, adhesion, and apoptotic signaling cascades, which led to mitochondrial aberrations and profound alterations in energy metabolism, increased susceptibility to reactive oxygen species generation, and apoptosis in luminal epithelium in NQO1(-/-) mice that were absent in wild-type mice. These pathophysiological changes led to the incidence of PBS in NQO1(-/-) mice. Altogether, the results demonstrate for the first time that NQO1 is an endogenous factor in protection against PBS. (C) 2012 Elsevier Inc. All rights reserved.