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1 型糖尿病大鼠模型血浆中金属蛋白酶组学和差异表达。

Metalloproteomic and differential expression in plasma in a rat model of type 1 diabetes.

机构信息

Department of Chemistry and Biochemistry, Institute of Bioscience, São Paulo State University (UNESP), Botucatu, SP, Brazil.

Department of Chemistry and Biochemistry, Institute of Bioscience, São Paulo State University (UNESP), Botucatu, SP, Brazil.

出版信息

Int J Biol Macromol. 2017 Nov;104(Pt A):414-422. doi: 10.1016/j.ijbiomac.2017.06.032. Epub 2017 Jun 8.

DOI:10.1016/j.ijbiomac.2017.06.032
PMID:28601647
Abstract

Type 1 diabetes is characterized by hyperglycemia, which in the chronic stage is associated with abnormalities in lipids, protein and, carbohydrate metabolism, as well as oxidative stress. New strategies for prevention and treatment are needed, as type 1 diabetes affects life quality and survival, and involves high-cost treatment. Proteomic and metalloproteomic studies can elucidate the functional and physiological aspects of biomolecules. In the present study, differential proteomics was used to identify potential biomarkers of diabetes in rat plasma associated with copper, selenium, zinc, and magnesium fractionation in control and diabetic rats, as well as diabetic rats treated with insulin. 2D-PAGE was used in the plasma protein fractionation; graphite furnace atomic absorption spectrometry (GFAAS) and flame atomic absorption spectrometry (FAAS) were used for quantitative determination of copper, magnesium, selenium, and zinc in the spots that showed different expression; and protein spots were characterized by electrospray ionization-tandem mass spectrometry (ESI-MS/MS) after tryptic digestion. ESI-MS/MS analysis characterized 35 different proteins, indicating alpha-1-macroglobulin and haptoglobulin as potential candidates as biomarkers for diabetes treated with insulin; also, 2'-deoxynucleoside 5'-phosphate N-hydrolase 1, transmembrane protein 11, serum amyloid P component, vitamin D-binding protein, and biliverdin reductase were identified as potential candidates as biomarkers for uncontrolled diabetes.

摘要

1 型糖尿病的特征是高血糖,在慢性阶段与脂质、蛋白质和碳水化合物代谢以及氧化应激的异常有关。需要新的预防和治疗策略,因为 1 型糖尿病会影响生活质量和生存,并且涉及高成本的治疗。蛋白质组学和金属蛋白质组学研究可以阐明生物分子的功能和生理方面。在本研究中,差异蛋白质组学用于鉴定与控制和糖尿病大鼠以及用胰岛素治疗的糖尿病大鼠中铜、硒、锌和镁分离相关的大鼠血浆中糖尿病的潜在生物标志物。2D-PAGE 用于血浆蛋白质的分离;石墨炉原子吸收光谱法(GFAAS)和火焰原子吸收光谱法(FAAS)用于定量测定显示不同表达的斑点中的铜、镁、硒和锌;经过胰蛋白酶消化后,通过电喷雾串联质谱法(ESI-MS/MS)对蛋白质斑点进行特征描述。ESI-MS/MS 分析鉴定了 35 种不同的蛋白质,表明α-1-巨球蛋白和触珠蛋白是用胰岛素治疗的糖尿病的潜在生物标志物候选物;此外,还鉴定出 2'-脱氧核苷 5'-磷酸 N-水解酶 1、跨膜蛋白 11、血清淀粉样蛋白 P 成分、维生素 D 结合蛋白和胆红素还原酶作为不受控制的糖尿病的潜在生物标志物候选物。

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