Poly(ADP-ribose) Polymerase is Involved in the Development of Diabetic Cystopathy via Regulation of Nuclear Factor Kappa B

OBJECTIVES To investigate whether overactivated Poly (ADP-ribose) polymerase (PARP) and subsequent activation of nuclear factor kappa B (NF-kappa B) correlate with the development of diabetic cystopathy via induction of bladder apoptosis. Diabetic cystopathy as a common complication of diabetes is frequently associated with increased oxidative stress and apoptosis of the bladder. PARP is activated by hyperglycemia-induced oxidative stress and plays a critical role in cell apoptosis and the development of diabetic complications, such as retinopathy and nephropathy. METHODS Sprague-Dawley rats were divided into 3 groups: control, diabetic, and diabetic treated with PARP inhibitor (DM + Vit-B3). Four weeks after induction of diabetes, the DM + Vit-B3 group was treated with PARP inhibitor (nicotinamide, 400 mg/kg/d) for 3 weeks. Bladder function was then assessed by conscious cystometry. The extent of oxidative stress and apoptosis, expression of poly(ADP-ribose) (PAR), NF-kappa B, phosphorylated inhibitor of NF-kappa B (I kappa B)-alpha, Bcl-2, and Bax in the bladder were also investigated. RESULTS Bladder dysfunction was strongly associated with increased oxidative stress and bladder apoptosis. In addition, the amount of PAR, phosphorylated I kappa B-alpha, expression of NF-kappa B, and Bax were significantly increased in diabetic rat bladder. Inhibition of PARP significantly reduced PARP activation and expression of NF-kappa B and Bax. As a result, bladder apoptosis was attenuated and bladder function was improved. CONCLUSIONS These results indicate that overactivated PARP and subsequent activation of NF-kappa B play important roles in the development of diabetic cystopathy via induction of bladder apoptosis. These findings may be applied in the development of novel therapies for patients with diabetic cystopathy. UROLOGY 77: 1265.e1-1265.e8, 2011. (C) 2011 Elsevier Inc.