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血浆血红素结合蛋白在 1 型糖尿病患者中上调:葡萄糖诱导的 ROS 的作用。

Hemopexin is up-regulated in plasma from type 1 diabetes mellitus patients: Role of glucose-induced ROS.

机构信息

Department of Pediatrics, Chiayi Christian Hospital, Chiayi, Taiwan.

出版信息

J Proteomics. 2012 Jun 27;75(12):3760-77. doi: 10.1016/j.jprot.2012.04.047. Epub 2012 May 8.

Abstract

Type 1 diabetes mellitus (T1DM) is an insulin-dependent metabolic disease in the world and often occurs in children and adolescents. Recent advances in quantitative proteomics offer potential for the discovery of plasma proteins as biomarkers for tracking disease progression and for understanding the molecular mechanisms of diabetes. Comparative proteomic analysis of the plasma proteomes from T1DM cases and healthy donors with lysine- and cysteine-labeling 2D-DIGE combining MALDI-TOF/TOF mass spectrometry revealed that 39 identified T1DM-associated plasma proteins showed significant changes in protein expression including hemopexin, and 41 in thiol reactivity. Further study showed that hemopexin can be induced in numerous cell lines by increasing the glucose concentration in the medium. Interestingly, glucose-induced hemopexin expression can be reduced by reactive oxygen species (ROS) scavengers such as glutathione, implying that hemopexin expression is linked to glucose-induced oxidative stress. In conclusion, the current work has identified potential T1DM biomarkers and one of these, hemopexin, can be modulated by glucose through a ROS-dependent mechanism.

摘要

1 型糖尿病(T1DM)是一种在世界范围内依赖胰岛素的代谢疾病,常发生于儿童和青少年。定量蛋白质组学的最新进展为发现血浆蛋白作为生物标志物来跟踪疾病进展和了解糖尿病的分子机制提供了可能。通过赖氨酸和半胱氨酸标记的 2D-DIGE 联合 MALDI-TOF/TOF 质谱对 T1DM 病例和健康供体的血浆蛋白质组进行比较蛋白质组学分析,显示 39 种鉴定出的与 T1DM 相关的血浆蛋白在蛋白质表达方面发生了显著变化,包括触珠蛋白,41 种具有巯基反应性。进一步的研究表明,通过增加培养基中的葡萄糖浓度,可以在许多细胞系中诱导触珠蛋白的表达。有趣的是,葡萄糖诱导的触珠蛋白表达可以被谷胱甘肽等活性氧(ROS)清除剂降低,这表明触珠蛋白的表达与葡萄糖诱导的氧化应激有关。总之,目前的工作已经确定了潜在的 T1DM 生物标志物,其中之一触珠蛋白可以通过 ROS 依赖的机制被葡萄糖调节。

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