BENIGN BLADDER DISEASE AND MITOCHONDRIAL FUNCTION

良性膀胱疾病和线粒体功能

• 批准号: 2444098
• 负责人: ALAN PAUL HUDSON
• 金额: $ 0.05万
• 依托单位: ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-26 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2444098
• 关键词: Krebs' cycle; adenosine triphosphate; autonomic agents; benign prostate hyperplasia; biological signal transduction; cellular pathology; clinical research; cytochrome oxidase; disease /disorder model; enzyme activity; gene expression; human tissue; laboratory rabbit; mitochondria; muscarinic receptor; polymerase chain reaction; potassium chloride; prostate preneoplastic state; urinary bladder disorder; urinary tract obstruction

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.

描述：良性前列腺引起的部分膀胱阻塞 增生与膀胱重量增加、 膀胱容量，膀胱顺应性和体外反应， 药理刺激。 在家兔中， 膀胱质量和功能的变化在14天后稳定。 在 代偿期，生化参数的改变，如乳酸 酸、CO2产生和丙酮酸代谢以及克雷布斯循环酶 活性表明线粒体能量产生受到影响。 而 梗阻膀胱的生理和生化变化已经被 特征，很少有研究的分子机制，这些 已经尝试过改变。 研究人员发现，在 阻塞后的第14天， 线粒体基因组在兔膀胱中减少了10倍;而TCA 循环酶的活性下降，细胞色素氧化酶不。 此外，虽然线粒体基因组拷贝数减少， 线粒体转录物保持接近正常，表明 线粒体转录的变化。 本 建议，调查人员计划定义表达的改变， 线粒体和核基因在代偿和失代偿期间 家兔部分梗阻后的时间。 他们还计划将 尿流动力学状态、膀胱质量和 对自主激动剂、场刺激和KCl的收缩反应。 这些研究将增加对膀胱癌的分子基础的理解， 梗阻后的功能障碍，并可能提供有用的信息， 设计新的治疗工具