HYPOXIA INDUCES GLUCOSE TRANSPORTER EXPRESSION IN ENDOTHELIAL-CELLS
HYPOXIA INDUCES GLUCOSE TRANSPORTER EXPRESSION IN ENDOTHELIAL-CELLS
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DOI：
10.1152/ajpcell.1992.263.2.c326
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发表时间：
1992-08-01
影响因子：
--
通讯作者：
STERN, D
中科院分区：
文献类型：
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作者：
LOIKE, JD;CAO, L;STERN, D
人体不同组织中的内皮细胞经常暴露在低氧条件下。为了研究持续低氧对内皮细胞能量代谢的影响，我们将牛主动脉和人脐静脉内皮细胞置于低氧(14 Mm Hg)环境中维持96h。在此，我们报道了与常氧细胞相比，维持在低氧环境下的内皮细胞葡萄糖转运活性上调，消耗更多的葡萄糖，产生更多的乳酸。低氧内皮细胞上调葡萄糖转运活性需要几个小时，这与红系/脑型葡萄糖转运体的mRNA和蛋白表达增加有关，而不是由于培养液中葡萄糖的耗尽。在常氧条件下，用氧化磷酸化抑制剂或解偶联剂(抗霉素、叠氮、二硝基苯酚)长期处理内皮细胞也可上调葡萄糖转运体的表达。这些结果表明，氧化代谢率降低可能是细胞代谢适应低氧的重要信号。此外，在我们对内皮细胞能量代谢的研究中，我们发现内皮细胞含有磷酸肌酸，并同时表达脑和肌肉肌酸激酶同工酶。
Endothelial cells in various tissues of the body are often exposed to hypoxic conditions. To examine the effects of sustained hypoxia on energy metabolism in endothelial cells, we have maintained bovine aortic and human umbilical vein endothelial cells in an atmosphere containing low oxygen concentrations (14 mmHg) for up to 96 h. We report here that endothelial cells maintained under these conditions upregulate their glucose transport activity, consume more glucose, and produce greater amounts of lactic acid than normoxic cells. Upregulation of glucose transport activity by hypoxic endothelial cells required several hours to occur, was associated with increased expression of mRNA and protein for the erythroid/brain form of the facilitative glucose transporter, and was not due to depletion of glucose from the medium. Prolonged treatment of endothelial cells with inhibitors or uncouplers of oxidative phosphorylation (antimycin, azide, dinitrophenol) under normoxic conditions also upregulated glucose transporter expression. These results suggest that reduced rates of oxidative metabolism may represent an important signal for cells to adapt metabolically to hypoxia. Furthermore, in our examination of endothelial cell energy metabolism, we discovered that endothelial cells contain phosphocreatine and express both the brain and muscle isozymes of creatine kinase.