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首页> 外文期刊>Biochemistry >3′-Sulfo-Lex Is Important for Regulation of Integrin Subunit αV
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3′-Sulfo-Lex Is Important for Regulation of Integrin Subunit αV

机译：3'-Sulfo-Lex对整联蛋白亚基αV的调节很重要

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摘要

Carbohydrate structures with a 30n-sulfo βGal linkage, such as 30n-sulfo-Lenxn, can be synthesized bynGal:3-O-sulfotransferase-2 (Gal3ST-2) catalysis, but little is known about their roles in many biologicalnprocesses. To investigate the role of Gal3ST-2 and its product 30n-sulfo-Lenxn, we depleted Gal3ST-2 via siRNAnand added exogenous Lewis-x trisaccharide 30n-sulfate sodium salt in human SMMC7721 hepatoma cells.nAfter siRNA transfection, a striking morphological change in SMMC7721 hepatoma cells from polygon tonshuttle shape and a significant decrease in the level of adhesion to sL-selectin, HUVEC, fibronectin,nvitronectin, and fibrinogen were observed. The expression of integrin subunit RV was markedly down-nregulated, and 30n-sulfated subunit RV almost disappeared in the transfectants. The level of cell surface integrinnRVβ3 was reduced simultaneously, although total subunit β3 underwent almost no change. After treatmentnwith exogenous Lewis-x 30n-sulfate, cellular integrin subunit RV was upregulated and the level of cell surfacenintegrin RVβ3 was elevated. Interestingly, knockdown of Gal3ST-2 expression effectively inhibited cellnproliferation, and the result was significantly correlated with the decrease in the levels of ILK, phosphorylatednAKT, and ERK. On the other hand, treatment with Lewis-x trisaccharide 30n-sulfate sodium salt greatlynupregulated the phosphorylation of AKT and ERK. Our results also indicated that downregulation ofnGal3ST-2 via siRNA transfection was associated with the decrease in the level of expression of anti-apoptoticnprotein, Bcl-2, with a consequent decrease in the ratios for Bcl-2 to Bax. By exposure to Lewis-x trisacchariden30n-sulfate sodium salt, the apoptotic response of cells was inhibited. Therefore, Gal3ST-2 and its product,n30n-sulfo-Lenxn, were involved in regulation of integrin subunit RV and might be associated with cancer cellnregulation.
机译：具有30n-磺基βGal键的碳水化合物结构（例如30n-磺基-Lenxn）可以通过nGal：3-O-磺基转移酶-2（Gal3ST-2）催化合成，但对其在许多生物过程中的作用知之甚少。为了研究Gal3ST-2及其产物30n-sulfo-Lenxn的作用，我们通过siRNAn去除了Gal3ST-2，并在人SMMC7721肝癌细胞中添加了外源的Lewis-x三糖30n-硫酸钠盐。观察到来自多边形扁桃体形状的SMMC7721肝癌细胞，并且与sL-选择素，HUVEC，纤连蛋白，n​​vitronectin和纤维蛋白原的粘附水平显着降低。整联蛋白亚基RV的表达显着下调，并且30n-硫酸化亚基RV在转染子中几乎消失。尽管总亚基β3几乎没有变化，但细胞表面整合素RVβ3的水平同时降低。用外源Lewis-x 30n-硫酸盐处理后，细胞整联蛋白亚基RV上调，细胞表面整联蛋白RVβ3水平升高。有趣的是，敲低Gal3ST-2表达可有效抑制细胞增殖，其结果与ILK，磷酸化nAKT和ERK含量的降低显着相关。另一方面，Lewis-x三糖30n-硫酸钠盐处理可大大上调AKT和ERK的磷酸化。我们的结果还表明，通过siRNA转染对nGal3ST-2的下调与抗凋亡蛋白Bcl-2的表达水平降低相关，因此Bcl-2与Bax的比例降低。通过暴露于Lewis-x三糖n30n-硫酸钠盐，可以抑制细胞的凋亡反应。因此，Gal3ST-2及其产物n30n-sulfo-Lenxn参与整联蛋白亚基RV的调控，并可能与癌细胞的调控有关。

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