BENIGN BLADDER DISEASE AND MITOCHONDRIAL FUNCTION

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DESCRIPTION: Partial bladder obstruction secondary to benign prostatic hyperplasia is associated with increased bladder mass, alterations in bladder capacity, in bladder compliance and in in vitro responses to pharmacological stimulations. In the rabbit, the obstruction-induced changes in the bladder mass and function stabilized after 14 days. In the compensated period, alterations in biochemical parameters such as lactic acid, CO2 production and pyruvate metabolism and Krebs cycle enzyme activities indicate that mitochondrial energy production is affected. While physiological and biochemical changes of the obstructed bladder have been characterized, few studies of molecular mechanisms underlying these alterations have been attempted. The investigators have shown that in the first 14 days post obstruction, the relative number of copies of the mitochondrial genome decreases by 10-fold in the rabbit bladder; while TCA cycle enzymes decline in activity, cytochrome oxidase does not. Furthermore, although mitochondrial genome copy number decreases, mitochondrial transcript remains near normal, suggesting an upregulation of mitochondrial transcription in the compensated period. In the present proposal, the investigators plan to define alterations in expression for mitochondrial and nuclear genes during the compensated and decompensated periods after partial obstruction in rabbit. They also plan to correlate the molecular findings with urodynamic status, bladder mass, and the contractile responses to autonomic agonists, field stimulation and KCl. These studies will increase understanding of the molecular basis for bladder dysfunction after obstruction and may provide useful information for designing new therapeutic tools.