Partial outlet obstruction of the rabbit bladder results in changes in the mitochondrial genetic system

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Abstract
In the rabbit, partial outlet obstruction of the urinary bladder results in significant changes in the physiology, cellular structure, and cellular metabolism of that organ. One of the most striking changes observed is a 50% decrease in oxidative metabolism. Here we investigate whether the function of the mitochondrial (mt) genetic system is altered in rabbit bladder tissue following partial outlet obstruction. Southern analyses of total DNA prepared from bladder tissue excised as a function of time after initiation of partial outlet obstruction showed that the relative number of copies of the mt genome decreases as much as 10-fold during the first 7 d after obstruction, and that this attenuated mt genome copy number is maintained until at least 14 d post-obstruction. Northern analyses, in contrast, showed that mtCOII and cytochromeb transcript levels initially decrease but recover to control levels by about 5 d after obstruction; that level is maintained through 14 d post-obstruction. Enzymatic analysis of cytochrome oxidase and NADH cytochromec reductase activities in obstructed bladder tissue gave results which paralleled the pattern in the mt RNA analyses. Surprisingly, transcript levels for the mt-related nuclearCOIV gene rapidly decreased to about 50% of control levels following obstruction and remained there until 14 d post-obstruction. These results indicate that partial outlet obstruction of the rabbit bladder leads to significant changes in the status and expression of the mt genetic system in bladder tissue. The maintenance of mt transcription under such circumstances may be an attempt to keep mt protein products at control levels, and this transcriptional adjustment may be responsible in part for the observed maintenance of bladder function during the initial (compensated) period which follows partial outlet obstruction.