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

Abstract

To investigate whether overactivated Poly (ADP-ribose) polymerase (PARP) and subsequent activation of nuclear factor kappa B (NF-κB) 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. 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-κB, phosphorylated inhibitor of NF-κB (IκB)-α, Bcl-2, and Bax in the bladder were also investigated. Bladder dysfunction was strongly associated with increased oxidative stress and bladder apoptosis. In addition, the amount of PAR, phosphorylated IκB-α, expression of NF-κB, and Bax were significantly increased in diabetic rat bladder. Inhibition of PARP significantly reduced PARP activation and expression of NF-κB and Bax. As a result, bladder apoptosis was attenuated and bladder function was improved. These results indicate that overactivated PARP and subsequent activation of NF-κB 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.