Glucose requirement for hypoxic accumulation of hypoxia-inducible factor-1α (HIF-1α)
Glucose requirement for hypoxic accumulation of hypoxia-inducible factor-1α (HIF-1α)
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DOI：
10.1016/j.canlet.2004.12.040
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发表时间：
2005-12-08
期刊：
影响因子：
9.7
通讯作者：
Flentje, M
中科院分区：
文献类型：
--
作者：
Vordermark, D;Kraft, P;Flentje, M
低氧诱导因子-1α(HIF-1α)既是肿瘤缺氧的潜在内源性标志物，也是治疗靶点，体外培养的FaDu人咽癌细胞HIF-1α蛋白水平升高与其耐低氧辐射能力增强有关。在这里，我们发现在FaDu异种移植中，无论是通过流式细胞仪还是Western印迹都没有检测到显著的HIF-1α蛋白积聚，尽管存在低氧(匹莫硝唑阳性，耐辐射)细胞。为了研究不同肿瘤微环境条件对缺氧性HIF-1α积聚的影响，我们在FaDu和HT1080人纤维肉瘤细胞中进行了体外低氧实验(0.1%02，24 h)，分别控制pH值(7.4vs.6.7)、葡萄糖(0-5.5 mM)和血清(0或10%)的可用性。低氧诱导的HIF-1α蛋白强烈依赖于葡萄糖的供应，在0.55 mM或更低的葡萄糖浓度下，两种细胞系中的HIF-1α蛋白的低氧诱导基本消失。这种葡萄糖效应在低氧反应元件(HRE)/增强绿色荧光蛋白(EGFP)报告实验中得到证实，并可能解释了缺氧肿瘤细胞中缺乏HIF-1α蛋白的原因。(C)2005爱思唯尔爱尔兰有限公司。保留所有权利。
Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is both a potential endogenous marker of tumor hypoxia and therapeutic target, and elevated HIF-1 alpha protein levels have been shown to be associated with increased hypoxic radiation resistance in FaDu human pharyngeal carcinoma cells in vitro. Here, we found that in FaDu xenografts, no significant HIF-1 alpha protein accumulation was detectable by either flow cytometry or Western blot, despite the presence of hypoxic (pimonidazole-positive, radiation resistant) cells. To investigate the effect of different tumor microenvironment conditions on hypoxic HIF-1 alpha accumulation, we performed in vitro hypoxia experiments (0.1% 02, 24 h) with manipulation of pH (7.4 vs. 6.7), glucose (0-5.5 mM) and serum (0 or 10%) availability in FaDu and HT 1080 human fibrosarcoma cells. Hypoxic induction of HIF-1 alpha protein was strongly dependent on glucose availability and largely abolished at 0.55 mM glucose or less in both cell lines. This glucose effect was confirmed in a hypoxia-responsive-element (HRE)/enhanced-green-fluorescent-protein (EGFP) reporter assay in transfected HT 1080 cells and possibly explains a lack of HIF-1 alpha protein in hypoxic tumor cells. (c) 2005 Elsevier Ireland Ltd. All rights reserved.