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脂多糖刺激 Caco-2 细胞中 UDP-葡糖醛酸基转移酶 1A6 同工型的表达。

Expression of UDP-glucuronosyltransferase 1A6 isoform in Caco-2 cells stimulated with lipopolysaccharide.

机构信息

Department of Human Anatomy and Histology, University of Bari, Bari, Italy.

出版信息

Innate Immun. 2010 Oct;16(5):302-9. doi: 10.1177/1753425909341909. Epub 2009 Aug 26.

Abstract

Glucuronidation is an important metabolic process of detoxification in all vertebrates. The reaction is catalyzed by a multigene family of UDP-glucuronosyltransferases (UGTs) able to convert many xenobiotics and endobiotics (hydrophobic substances) to inactive, water-soluble glucuronides. The UGTs play a protective role, facilitating the elimination of potentially toxic metabolites via urine, bile and feces; therefore, impairment of UGTs may have important toxicological consequences. The regulation of UGTs during bacterial infection or inflammation is not well described. In this study, we investigated the in vitro effect of lipopolysaccharide (LPS) on the expression of the UGT1A6 isoform in human colon carcinoma Caco-2 cells. Results demonstrated a significant down-regulation of UGT1A6 expression, both in terms of mRNA and protein levels, and a reduced UGT activity after LPS exposure of cell cultures, suggesting a role for endotoxins on UGT regulation mechanisms.

摘要

糖基化是所有脊椎动物解毒的重要代谢过程。该反应由多基因家族的 UDP-葡糖醛酸基转移酶 (UGTs) 催化,能够将许多外源物和内源性物质(疏水性物质)转化为无活性的水溶性葡糖苷酸。UGTs 发挥保护作用,通过尿液、胆汁和粪便促进潜在有毒代谢物的消除;因此,UGTs 的损伤可能具有重要的毒理学后果。细菌感染或炎症期间 UGTs 的调节尚不清楚。在这项研究中,我们研究了脂多糖 (LPS) 对人结肠癌细胞 Caco-2 中 UGT1A6 同工型表达的体外影响。结果表明,LPS 暴露于细胞培养物后,UGT1A6 的表达在 mRNA 和蛋白质水平上均显著下调,UGT 活性降低,提示内毒素在 UGT 调节机制中的作用。

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