Nevel-McGarvey C A, Levin R M, Hudson A P
Department of Microbiology and Immunology, MCP-Hahnemann School of Medicine, Philadelphia, PA 19104, USA.
Mol Cell Biochem. 1997 Aug;173(1-2):95-102.
Using the rabbit model, we showed that partial outlet obstruction of the urinary bladder causes significant changes in the status and expression of the mitochondrial (mt) genetic system in bladder smooth muscle immediately after obstruction is initiated. Here we investigate quantitatively the severity of the mt genetic response to partial outlet obstruction in both short- and long-term obstructed rabbits. Based on previous functional studies, bladders with mass < 6 fold greater than control were considered compensated; bladders with mass > 6 fold that of control were considered decompensated. Analyses of DNA from compensated rabbit bladders showed that relative mt genome copy number decreased to 30% of control values. Transcript analyses for these samples showed 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; mt transcripts progressively decreased in these samples by as much as 30 fold. In contrast, transcription of a mt-related nuclear gene decreased 3-9 fold in compensated bladders but increased 10-30 fold in decompensated bladders. Activity for the cytochrome oxidase complex, and for the mt enzyme citrate synthase, decreased steadily with increasing bladder hypertrophy. These data suggest that bladder dysfunction following partial outlet obstruction is mediated partly by a significant loss in mt and mt-related nuclear gene coordination.
利用兔模型，我们发现膀胱出口部分梗阻在梗阻开始后立即会导致膀胱平滑肌中线粒体（mt）遗传系统的状态和表达发生显著变化。在此，我们定量研究短期和长期梗阻兔中mt遗传对膀胱出口部分梗阻反应的严重程度。基于先前的功能研究，质量比对照大6倍以内的膀胱被认为是代偿性的；质量比对照大6倍以上的膀胱被认为是失代偿性的。对代偿性兔膀胱DNA的分析表明，相对mt基因组拷贝数降至对照值的30%。对这些样本的转录分析表明，mt RNA水平增加3倍以补偿较低的模板拷贝数。对失代偿性膀胱的分析表明，mt基因组拷贝数增加至对照水平的约90%；这些样本中的mt转录本逐渐减少多达30倍。相比之下，mt相关核基因的转录在代偿性膀胱中减少3 - 9倍，但在失代偿性膀胱中增加10 - 30倍。细胞色素氧化酶复合体以及mt酶柠檬酸合酶的活性随着膀胱肥大的增加而稳步下降。这些数据表明，膀胱出口部分梗阻后的膀胱功能障碍部分是由mt与mt相关核基因协调的显著丧失介导的。
