Oxidative stress status accompanying diabetic bladder cystopathy results in the activation of protein degradation pathways.
Oxidative stress status accompanying diabetic bladder cystopathy results in the activation of protein degradation pathways.
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DOI：
10.1111/j.1464-410x.2010.09655.x
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发表时间：
2011-05
影响因子：
4.5
通讯作者：
Davies KD
中科院分区：
文献类型：
--
作者：
Kanika ND;Chang J;Tong Y;Tiplitsky S;Lin J;Yohannes E;Tar M;Chance M;Christ GJ;Melman A;Davies KD
研究氧化应激在糖尿病性膀胱病发生中的作用。使用微阵列分析对非糖尿病大鼠和链脲佐菌素 (STZ) 诱导的 2 个月大糖尿病大鼠膀胱中的基因表达进行比较。通过分析谷胱甘肽 S-转移酶活性、脂质过氧化以及蛋白质的羰基化和亚硝基化，研究了膀胱中氧化应激的证据。使用蛋白质印迹分析评估蛋白质降解途径的活性。对整体基因表达的分析表明，STZ 诱导的糖尿病的逼尿肌平滑肌组织中参与活性氧产生或调节的靶标显着富集 (P = 1.27 × 10−10)。微阵列分析显示糖尿病膀胱中氧化应激标志物均显着增加，从而证实了这一点。据推测，氧化应激的后遗症将是蛋白质损伤和细胞凋亡增加。与对照组相比，糖尿病膀胱中参与蛋白质降解的两种关键蛋白（Nedd4 和 LC3B）分别大幅上调 12.2 ± 0.76 和 4.4 ± 1.0 倍，并且凋亡诱导蛋白 BAX 上调 6.76 ± 0.76 倍，从而证实了这一点。总体而言，本研究中获得的结果增加了越来越多的证据，表明糖尿病性膀胱病与平滑肌细胞的氧化损伤有关，并导致蛋白质损伤和细胞凋亡途径激活，可能导致膀胱功能恶化。
To investigate the role that oxidative stress plays in the development of diabetic cystopathy. Comparative gene expression in the bladder of non-diabetic and streptozotocin (STZ)-induced 2-month-old diabetic rats was carried out using microarray analysis. Evidence of oxidative stress was investigated in the bladder by analyzing glutathione S-transferase activity, lipid peroxidation, and carbonylation and nitrosylation of proteins. The activity of protein degradation pathways was assessed using western blot analysis. Analysis of global gene expression showed that detrusor smooth muscle tissue of STZ-induced diabetes undergoes significant enrichment in targets involved in the production or regulation of reactive oxygen species (P = 1.27 × 10−10). The microarray analysis was confirmed by showing that markers of oxidative stress were all significantly increased in the diabetic bladder. It was hypothesized that the sequelae to oxidative stress would be increased protein damage and apoptosis. This was confirmed by showing that two key proteins involved in protein degradation (Nedd4 and LC3B) were greatly up-regulated in diabetic bladders compared to controls by 12.2 ± 0.76 and 4.4 ± 1.0-fold, respectively, and the apoptosis inducing protein, BAX, was up-regulated by 6.76 ± 0.76-fold. Overall, the findings obtained in the present study add to the growing body of evidence showing that diabetic cystopathy is associated with oxidative damage of smooth muscle cells, and results in protein damage and activation of apoptotic pathways that may contribute to a deterioration in bladder function.