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链脲佐菌素诱导糖尿病大鼠胰腺蛋白质组谱的改变。

Alteration of the proteome profile of the pancreas in diabetic rats induced by streptozotocin.

机构信息

Yue Yang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, P.R. China.

出版信息

Int J Mol Med. 2011 Aug;28(2):153-60. doi: 10.3892/ijmm.2011.696. Epub 2011 May 9.

DOI:10.3892/ijmm.2011.696
PMID:21567075
Abstract

Type 1 diabetes mellitus (T1DM) is receiving increased attention. To obtain a better understanding of the mechanism underlying T1DM, we performed a proteomic study on a rat model induced by streptozotocin. Pancreatic proteins were separated by two-dimensional gel electrophoresis. Eighteen protein spots were differentially expressed (P<0.05) with 2-fold or more increased or decreased intensity in the diabetic rats as compared with controls, of which 11 protein spots were up-regulated and 7 protein spots were down-regulated. These protein spots were successfully identified by liquid chromatography-electrospray ionization tandem mass spectrometry. The 60 kDa heat shock protein, the carbonyl reductase 1 (Cbr1), the hydroxyacyl-CoA dehydrogenase, Δ(3,5),Δ(2,4)-dienoyl-CoA isomerase, the elongation factor 1-δ, the 26S protease regulatory subunit 7 and the transitional endoplasmic reticulum ATPase were up-regulated, while the 78 kDa glucose-regulated protein, peroxiredoxin 4 and plakoglobin were down-regulated. The expression change of Cbr1 which is closely related to diabetic complications was further validated by western blotting. Our results and those of the bioinformatics analysis suggest that oxidative stress, the Wnt pathway, fatty acid degradation and glucose transport may be closely related to T1DM.

摘要

1 型糖尿病(T1DM)受到越来越多的关注。为了更好地了解 T1DM 的发病机制,我们对链脲佐菌素诱导的大鼠模型进行了蛋白质组学研究。通过二维凝胶电泳分离胰腺蛋白。与对照组相比,糖尿病大鼠中有 18 个蛋白点差异表达(P<0.05),其强度增加或减少了 2 倍以上,其中 11 个蛋白点上调,7 个蛋白点下调。这些蛋白点通过液相色谱-电喷雾串联质谱成功鉴定。60 kDa 热休克蛋白、羰基还原酶 1(Cbr1)、羟基酰基辅酶 A 脱氢酶、Δ(3,5)、Δ(2,4)-二烯酰基辅酶 A 异构酶、延伸因子 1-δ、26S 蛋白酶调节亚基 7 和过渡内质网 ATP 酶上调,而 78 kDa 葡萄糖调节蛋白、过氧化物还原酶 4 和斑联蛋白下调。通过 Western 印迹进一步验证了与糖尿病并发症密切相关的 Cbr1 的表达变化。我们的结果和生物信息学分析表明,氧化应激、Wnt 通路、脂肪酸降解和葡萄糖转运可能与 T1DM 密切相关。

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