Inhibitory effect of HIV-1 Tat protein on the sodium-D-glucose symporter of human intestinal epithelial cells
Inhibitory effect of HIV-1 Tat protein on the sodium-D-glucose symporter of human intestinal epithelial cells
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DOI：
10.1097/01.aids.0000198088.85572.68
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发表时间：
2006-01-02
期刊：
影响因子：
3.8
通讯作者：
Guarino, A
中科院分区：
文献类型：
--
作者：
Canani, RB;De Marco, G;Guarino, A
目的：hiv -1相关肠道功能障碍的病理生理机制在很大程度上是未知的。我们之前发现HIV-1产生的反激活因子肽（Tat）诱导离子分泌并抑制人类肠细胞的细胞增殖。由于糖吸收不良是艾滋病患者的常见特征，我们评估了Tat是否会抑制肠道葡萄糖吸收。设计和方法：我们测量了Na+- d -葡萄糖同体（SGLT-1）的活性，并测定了其在Caco-2细胞中的表型表达，分别在Tat存在和不存在的情况下，在非代谢放射性标记葡萄糖类似物的摄取实验中，以及通过western blot分析。α -微管蛋白染色法研究Tat对细胞结构的影响。结果：乙二胺对人肠细胞葡萄糖摄取的抑制呈剂量依赖性。抗tat多克隆抗体和l型Ca2+通道激动剂Bay K8644可阻止这种作用。细胞裂解物和刷边膜制备物的Western blot分析显示Tat诱导SGLT-1错选。这也引起了α -微管蛋白染色的急剧下降，这表明细胞骨架组织的破坏。结论：SGLT-1分拣不当会严重损害肠道葡萄糖吸收。这一结果表明Tat直接参与了艾滋病相关的肠道功能障碍。(C) 2006 Lippincott Williams & Wilkins。
Objective: The pathophysiology of HIV-1-related intestinal dysfunction is largely unknown. We previously found that the transactivator factor peptide (Tat) produced by HIV-1 induces ion secretion and inhibits cell proliferation in human enterocytes. Because sugar malabsorption is a frequent feature in AIDS patients, we evaluated whether Tat inhibits intestinal glucose absorption.Design and methods: We measured Na+-D-glucose symporter (SGLT-1) activity and determined its phenotypic expression in Caco-2 cells, in the presence and absence of Tat, in uptake experiments using a non-metabolized radiolabelled glucose analogue, and by western blot analysis, respectively. alpha-Tubulin staining was used to study the effects exerted by Tat on cell structure.Results: Tat dose dependently inhibited glucose uptake by human enterocytes. This effect was prevented by anti-Tat polyclonal antibodies and by L-type Ca2+ channels agonist Bay K8644. Western blot analysis of cellular lysates and brush-border membrane preparations showed that Tat induced SGLT-1 missorting. Tat also caused a dramatic decrease in alpha-tubulin staining, which indicates dysruption of the cytoskeleton organization.Conclusions: Tat acutely impairs intestinal glucose absorption through SGLT-1 missorting. This result indicates that Tat is directly involved in AIDS-associated intestinal dysfunction. (C) 2006 Lippincott Williams & Wilkins.