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从凡纳滨对虾(Litopenaeus vannamei)中提取的一种具有抗凝血酶活性的独特硫酸软骨素,可调节急性炎症。

A further unique chondroitin sulfate from the shrimp Litopenaeus vannamei with antithrombin activity that modulates acute inflammation.

机构信息

Programa de Pós-graduação em Bioquímica e Biologia Molecular, Departamento de Bioquímica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil; Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, United Kingdom.

Programa de Pós-graduação em Bioquímica e Biologia Molecular, Departamento de Bioquímica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil; Faculdade de Ciências da Saúde do Trairi, Universidade Federal do Rio Grande do Norte, Santa Cruz, RN, Brazil.

出版信息

Carbohydr Polym. 2019 Oct 15;222:115031. doi: 10.1016/j.carbpol.2019.115031. Epub 2019 Jun 28.

Abstract

The detailed structure of a further Chondroitin Sulfate from Litopenaeus vannamei shrimp (sCS) is described. The backbone structure was established by H/C NMR, which identified 3-O-sulfated GlcA, 4-O-sulfated GalNAc, 6-O-sulfated GalNAc, and 4,6-di-O-sulfated GalNAc residues. GlcA is linked to GalNAc 4,6 di S and GlcA 3S is linked to GalNAc 4S, GalNAc 4,6 di-S and GalNAc6S residues. The anticoagulant properties of this sCS were evaluated by activated partial thromboplastin time, anti-IIa, anti-Xa and anti-heparin cofactor II-mediated activities, and sCS failed to stabilise antithrombin in a fluoresence shift assay. The anti-inflammatory effect of sCS was explored using a model of acute peritonitis, followed by leukocyte count and measurement of the cytokines, IL-1β, IL-6 and TNF-α. The compound showed low clotting effects, but high anti-IIa activity and HCII-mediated thrombin inhibition. Its anti-inflammatory effect was shown by leukocyte recruitment inhibition and a decrease in pro-inflammatory cytokine levels. Although the biological role of sCS remains unknown, its properties indicate that it is suitable for studies of multi-potent molecules obtained from natural sources.

摘要

详细描述了凡纳滨对虾(Litopenaeus vannamei)虾软骨素硫酸盐(sCS)的结构。通过 H/C NMR 确定了其骨架结构,鉴定出 3-O-硫酸化 GlcA、4-O-硫酸化 GalNAc、6-O-硫酸化 GalNAc 和 4,6-二-O-硫酸化 GalNAc 残基。GlcA 与 GalNAc 4,6 二 S 和 GlcA 3S 与 GalNAc 4S、GalNAc 4,6 二 S 和 GalNAc6S 残基相连。通过激活部分凝血活酶时间、抗 IIa、抗 Xa 和抗肝素辅因子 II 介导的活性评估了该 sCS 的抗凝特性,sCS 未能在荧光转移测定中稳定抗凝血酶。通过急性腹膜炎模型研究了 sCS 的抗炎作用,然后进行白细胞计数和细胞因子 IL-1β、IL-6 和 TNF-α 的测量。该化合物具有较低的凝血作用,但具有较高的抗 IIa 活性和 HCII 介导的凝血酶抑制作用。其抗炎作用表现为白细胞募集抑制和促炎细胞因子水平降低。尽管 sCS 的生物学作用尚不清楚,但它的特性表明它适合于研究从天然来源获得的多功能分子。

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