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定量测定银屑病中结合珠蛋白糖型变体。

Quantitative determination of haptoglobin glycoform variants in psoriasis.

机构信息

Dipartimento di Patologia Sistematica - Sezione di Dermatologia, Università di Napoli Federico II, Italy.

出版信息

Biol Chem. 2010 Dec;391(12):1429-39. doi: 10.1515/BC.2010.146.

DOI:10.1515/BC.2010.146
PMID:21087091
Abstract

Haptoglobin is an acute phase glycoprotein, secreted by hepatocytes and other types of cells including keratinocytes. Haptoglobin has been suggested to impair the immune response, inhibit gelatinases in the extracellular matrix and promote angiogenesis, but its role in psoriasis is obscure to date. Changes in haptoglobin glycan structure were observed in several diseases. The aim of this study was to investigate whether haptoglobin displays glycan variations in psoriasis. We found that the pattern of plasma haptoglobin glycoforms, following two-dimensional electrophoresis, exhibited significant quantitative differences in spot intensities between patients and controls. Quantitative and qualitative differences in glycan mass, between patients and controls, were found by mass spectrometry of glycopeptides from tryptic digests of protein isolated from both patients and controls. The number of distinct fucosylated glycoforms of peptides NLFLNHSENATAK and MVSHHNLTTGATLINEQWLLTTAK was higher in patients than in controls, but no fucosylated glycan was detected on peptide VVLHPNYSQ-VDIGLIK in either case. The number of peptides with distinct triantennary and tetraantennary glycans was higher in patients than in controls. Abundance or structure of specific glycans, which are present in haptoglobin from patients and are different or missing in normal haptoglobin, might be associated with disease activity.

摘要

触珠蛋白是一种急性相糖蛋白,由肝细胞和包括角质形成细胞在内的其他类型细胞分泌。触珠蛋白被认为会损害免疫反应、抑制细胞外基质中的明胶酶并促进血管生成,但迄今为止其在银屑病中的作用尚不清楚。在几种疾病中观察到触珠蛋白糖链结构的变化。本研究旨在探讨触珠蛋白在银屑病中是否存在糖型变化。我们发现,经二维电泳后,血浆触珠蛋白糖型的模式在患者和对照组之间的斑点强度上表现出显著的定量差异。通过对来自患者和对照组的蛋白质进行胰蛋白酶消化后获得的糖肽进行质谱分析,发现患者和对照组之间在聚糖质量上存在定量和定性差异。与对照组相比,肽 NLFLNHSENATAK 和 MVSHHNLTTGATLINEQWLLTTAK 的独特岩藻糖基化糖型数量更高,但在两种情况下均未检测到肽 VVLHPNYSQ-VDIGLIK 的岩藻糖基化糖。具有独特三触角和四触角聚糖的肽数量在患者中高于对照组。存在于患者触珠蛋白中的特定聚糖的丰度或结构与疾病活动相关,而这些聚糖在正常触珠蛋白中不存在或缺失。

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