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人直肠癌中蛋白聚糖的组成和结构改变,特别提及多功能蛋白聚糖和核心蛋白聚糖。

Compositional and structural alterations of proteoglycans in human rectum carcinoma with special reference to versican and decorin.

作者信息

Tsara Marina E, Theocharis Achilleas D, Theocharis Dimitrios A

机构信息

Laboratory of Biological Chemistry, School of Medicine, University of Patras, 261 10 Greece.

出版信息

Anticancer Res. 2002 Sep-Oct;22(5):2893-8.

Abstract

This study indicated that human normal rectum (HNR) and human rectum carcinoma (HRC) contained three populations of proteoglycans (PGs). About 63% of the HNR PGs, in terms of uronic acid, were heparan sulfate proteoglycans (HSPGs) of M(r) 500,000 with HS side-chains of M(r) 35,000. The other two populations were versican (29%) and decorin (8%) of M(r) 715,000 and 90,000, respectively, bearing mainly dermatan sulfate (DS) (73%) and chondroitin sulfate (CS) (27%) chains of M(r) 24-26,000 and 20-22,000, respectively. In contrast, in terms of uronic acid, HRC contained 2-fold amounts of PGs. The majority of these PGs (87%) were versican and decorin of lower hydrodynamic size (500,000 and 70,000, respectively) than in HNR, with CS as prominent GAG (70%) in both types of PG. The M(r) of CS and DS chains in these PGs was 12-14,000 and 14-16,000, respectively. The remaining portion (13%) of PG was HSPGs of lower hydrodynamic size (300,000) with smaller HS chains (29,000) than HSPGs of HNR. Moreover, the molar concentrations of versican and decorin estimated from PG-derived protein contents represented a significant, but disproportionate increase, about 5-fold and 8-fold, respectively. The sulfation pattern of rectum carcinoma-associated versican and decorin was significantly altered mainly in containing (62%) 6-sulfated disaccharides and a significant proportion (10%) of non-sulfated disaccharides. DS chains of the tumor-associated versican and decorin contained decreased amounts of iduronic acid. On the metabolic level, the abnormally high production of versican and decorin in this malignant tumor suggests a dramatic modification in their biosynthetic steps at both translational and posttranslational levels.

摘要

本研究表明,人类正常直肠(HNR)和人类直肠癌(HRC)含有三种蛋白聚糖(PGs)群体。就糖醛酸而言,约63%的HNR PGs是分子量为500,000的硫酸乙酰肝素蛋白聚糖(HSPGs),其硫酸乙酰肝素(HS)侧链分子量为35,000。另外两个群体分别是分子量为715,000的多功能蛋白聚糖(versican,占29%)和分子量为90,000的核心蛋白聚糖(decorin,占8%),它们主要带有分子量分别为24 - 26,000和20 - 22,000的硫酸皮肤素(DS)(73%)和硫酸软骨素(CS)(27%)链。相比之下,就糖醛酸而言,HRC中PGs的含量是HNR的2倍。这些PGs中的大多数(87%)是多功能蛋白聚糖和核心蛋白聚糖,其流体力学尺寸比HNR中的小(分别为500,000和70,000),两种类型的PG中均以CS作为主要的糖胺聚糖(GAG,占70%)。这些PGs中CS和DS链的分子量分别为12 - 14,000和14 - 16,000。其余部分(13%)的PG是流体力学尺寸较小(300,000)且HS链比HNR的HSPGs小(29,000)的HSPGs。此外,从PG衍生的蛋白质含量估算的多功能蛋白聚糖和核心蛋白聚糖的摩尔浓度有显著但不成比例的增加,分别约为5倍和8倍。直肠癌相关的多功能蛋白聚糖和核心蛋白聚糖的硫酸化模式发生了显著改变,主要表现为含有(62%)6 - 硫酸化二糖和相当比例(10%)的非硫酸化二糖。肿瘤相关的多功能蛋白聚糖和核心蛋白聚糖的DS链中艾杜糖醛酸含量减少。在代谢水平上,这种恶性肿瘤中多功能蛋白聚糖和核心蛋白聚糖的异常高产量表明它们在翻译和翻译后水平的生物合成步骤发生了显著改变。

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