TRANSCRIPTION OF MITOCHONDRIAL AND MITOCHONDRIA-RELATED NUCLEAR GENESIN RABBIT BLADDER FOLLOWING PARTIAL OUTLET OBSTRUCTION

Using the rabbit model, we showed that partial outlet obstruction of t he urinary bladder causes significant changes in the status and expres sion of the mitochondrial (mt) genetic system in bladder smooth muscle immediately after obstruction is initiated. Here we investigate quant itatively the severity of the mt genetic response to partial outlet ob struction in both short-and long-term obstructed rabbits. Based on pre vious functional studies, bladders with mass < 6 fold greater than con trol were considered compensated; bladders with mass > 6 fold that of control were considered decompensated. Analyses of DNA from compensate d rabbit bladders showed that relative mt genome copy number decreased to 30% of control values. Transcript analyses for these samples showe d that mt RNA levels increased 3 fold to compensate for lower template copy number. Analysis of decompensated bladders demonstrated that mt genome copy number increased to approximately 90% of control levels; m t transcripts progressively decreased in these samples by as much as 3 0 fold. In contrast, transcription of a mt-related nuclear gene decrea sed 3-9 fold in compensated bladders but increased 10-30 fold in decom pensated bladders. Activity for the cytochrome oxidase complex, and fo r the mt enzyme citrate synthase, decreased steadily with increasing b ladder hypertrophy. These data suggest that bladder dysfunction follow ing partial outlet obstruction is mediated partly by a significant los s in mt and mt-related nuclear gene coordination.