Cho William C, Yip Tai-Tung, Chung Wai-Shing, Leung Albert W, Cheng Christopher H, Yue Kevin K
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong.
J Cell Biochem. 2006 Sep 1;99(1):256-68. doi: 10.1002/jcb.20923.
Diabetes mellitus (DM) is a chronic progressive disease that often results in microvascular and macrovascular complications, yet its pathogenesis is not clear. Automated proteomic technology, coupled with powerful bioinformatics and statistical tools, can provide new insights into the molecular alterations implicated in DM. Following our previous findings of redox changes in the eye and aorta of diabetic rats, as well as the activities of different antioxidant enzymes during the development of DM, this study is further launched to find potential biomarkers by comparing the serum and tissue samples of 26 diabetic rats (8 weeks after streptozotocin [STZ] administration) with 29 normal controls using surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) technology. Eight potential biomarkers were found in the serum, one potential biomarker was found in the kidney and eye, respectively, whereas three potential biomarkers were discovered in the aorta. One of the serum biomarker candidates was found to match the C-reactive protein (CRP) in the Swiss-Prot knowledgebase. Further validation has been conducted by ELISA kit to confirm the role of CRP during the development of DM. To conclude, the increased level of CRP in diabetic serum demonstrated in this study indicates that the development of DM is associated with inflammation. This is also the first report demonstrating that some potential lysate biomarkers in the kidney, eye, and aorta may be involved in the development of diabetes and its complications. Further identification and evaluation of these potential biomarkers will help unravel the underlying mechanisms of the disease.
糖尿病(DM)是一种慢性进行性疾病,常导致微血管和大血管并发症,但其发病机制尚不清楚。自动化蛋白质组学技术,结合强大的生物信息学和统计工具,可为糖尿病相关的分子改变提供新的见解。基于我们之前关于糖尿病大鼠眼睛和主动脉氧化还原变化以及糖尿病发展过程中不同抗氧化酶活性的研究结果,本研究进一步开展,通过表面增强激光解吸/电离飞行时间质谱(SELDI-TOF MS)技术,比较26只糖尿病大鼠(链脲佐菌素[STZ]给药8周后)与29只正常对照的血清和组织样本,以寻找潜在的生物标志物。在血清中发现了8种潜在生物标志物,在肾脏和眼睛中分别发现了1种潜在生物标志物,而在主动脉中发现了3种潜在生物标志物。血清生物标志物候选物之一被发现与瑞士蛋白质数据库中的C反应蛋白(CRP)匹配。通过ELISA试剂盒进行了进一步验证,以确认CRP在糖尿病发展过程中的作用。总之,本研究中糖尿病血清中CRP水平升高表明糖尿病的发展与炎症有关。这也是首次报道表明肾脏、眼睛和主动脉中的一些潜在裂解物生物标志物可能参与糖尿病及其并发症的发展。对这些潜在生物标志物的进一步鉴定和评估将有助于揭示该疾病的潜在机制。