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Oxidative stress status accompanying diabetic bladder cystopathy results in the activation of protein degradation pathways
Author(s) -
Kanika Nirmala D.,
Chang Jinsook,
Tong Yuehong,
Tiplitsky Scott,
Lin Juan,
Yohannes Elizabeth,
Tar Moses,
Chance Mark,
Christ George J.,
Melman Arnold,
Davies Kelvin D.
Publication year - 2011
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2010.09655.x
Subject(s) - oxidative stress , streptozotocin , diabetes mellitus , lipid peroxidation , western blot , microarray analysis techniques , glutathione , oxidative phosphorylation , protein carbonylation , endocrinology , medicine , chemistry , gene expression , biochemistry , gene , enzyme
What’s known on the subject? and What does the study add? Diabetes is a common precursor for ladder pathology, including detrusor overactivity and cystopathy. There is preliminary, but increasing evidence, suggesting that oxidative stress plays a significant role in the development of diabetic complications including its affect on the bladder. In the present study we investigated the effect of streptozotocin induced‐diabetes in rats on the global expression of genes in the rat bladder using microarray analysis, and combined this data with our previously reported study looking at changes in protein levels using proteomics. This analysis demonstrated that markers of oxidative stress were significantly increased in the diabetic bladder. Overall, our work adds to the growing body of evidence that diabetic cystopathy is associated with oxidative damage of smooth muscle cells, and results in protein damage and activation of apoptotic pathways which may contribute to a deterioration in bladder function. OBJECTIVE• To investigate the role that oxidative stress plays in the development of diabetic cystopathy.MATERIALS AND METHODS• 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.RESULTS• 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.CONCLUSION• 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.