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链脲佐菌素诱导的糖尿病大鼠胰腺对真菌多糖治疗反应的蛋白质组学和转录组学分析。

Proteomic and transcriptomic analysis for streptozotocin-induced diabetic rat pancreas in response to fungal polysaccharide treatments.

作者信息

Kim Sang Woo, Hwang Hye Jin, Baek Yu Mi, Lee Sung Hak, Hwang Hee Sun, Yun Jong Won

机构信息

Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk, Korea.

出版信息

Proteomics. 2008 Jun;8(11):2344-61. doi: 10.1002/pmic.200700779.

DOI:10.1002/pmic.200700779
PMID:18452227
Abstract

In an attempt to search for novel biomarkers for monitoring diabetes prognosis, we examined the influence of the hypoglycemic fungal extracellular polysaccharides (EPS) on the differential change in pancreatic proteome and transcriptome in streptozotocin (STZ)-induced diabetic rats using 2-DE-based protein mapping and oligonucleotide microarray analysis. The 2-DE system separated more than 2000 individual spots, demonstrating that 34 proteins out of about 500 matched spots were differentially expressed. A total of 22 overexpressed and 12 underexpressed proteins in 2-DE map were observed (p<0.05) between the healthy and diabetic rats, of which 26 spots were identified by PMF analysis. Of these, significant down regulation of carbonyl reductase (Cbr), hydroxymethylglutaryl-CoA synthase (HMGCS), and putative human mitogen-activated protein kinase activator with WD repeats-binding protein (MAWDBP) in diabetic pancreas were reported for the first time in this study. When treated with EPS, all these four proteins were reverted to normal levels. The microarray analysis revealed that 96 out of 1272 genes were down- or up-regulated in the diabetic rats and the altered transcript levels of many of these genes were reversed after EPS treatment. In particular, ROS generation in rat islets was significantly increased after STZ treatment, thereafter EPS treatment was likely to play a preventive role in beta-cell destruction mediated by STZ. Taken together, EPS may act as a potent regulator of gene expression for a wide variety of genes in diabetic rats, particularly in antioxidative stress, insulin biosynthesis, and cell proliferation.

摘要

为了寻找用于监测糖尿病预后的新型生物标志物,我们使用基于二维电泳的蛋白质图谱和寡核苷酸微阵列分析,研究了降血糖真菌胞外多糖(EPS)对链脲佐菌素(STZ)诱导的糖尿病大鼠胰腺蛋白质组和转录组差异变化的影响。二维电泳系统分离出2000多个单个斑点,表明在约500个匹配斑点中,有34种蛋白质表达存在差异。在健康大鼠和糖尿病大鼠之间,二维电泳图谱中共观察到22种过表达蛋白和12种低表达蛋白(p<0.05),其中26个斑点通过肽质量指纹图谱分析得以鉴定。在本研究中,首次报道了糖尿病胰腺中羰基还原酶(Cbr)、羟甲基戊二酰辅酶A合酶(HMGCS)以及具有WD重复序列结合蛋白的假定人类丝裂原活化蛋白激酶激活剂(MAWDBP)的显著下调。用EPS处理后,所有这四种蛋白质均恢复到正常水平。微阵列分析显示,1272个基因中有96个在糖尿病大鼠中发生了下调或上调,并且这些基因中许多基因的转录水平变化在EPS处理后得到了逆转。特别是,STZ处理后大鼠胰岛中的活性氧生成显著增加,此后EPS处理可能在STZ介导的β细胞破坏中发挥预防作用。综上所述,EPS可能作为糖尿病大鼠多种基因表达的有效调节剂,尤其是在抗氧化应激、胰岛素生物合成和细胞增殖方面。

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