Department of Physiology, Aichi Medical University, 1-1 Yazako-Karimata, Nagakute-City, Aichi, 4801165, Japan.
Department of Biochemistry and Molecular Biology, Mawlana Bhashani Science and Technology University, Santosh, Tangail, 1902, Bangladesh.
J Physiol Sci. 2020 Sep 22;70(1):44. doi: 10.1186/s12576-020-00773-y.
Glucose uptake and adenosine triphosphate (ATP) generation are important for the survival and growth of endothelial cells. An increase of glucose uptake under hypoxia was previously shown to be associated with the increased expression of glucose transporters (GLUTs). However, the regulation of GLUT trafficking to the cell surface has not been examined in detail. Here, we report the characterization of GLUT1 translocation to the plasma membrane during hypoxia in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were exposed to hypoxia (1% O) for 12 h, which significantly induced GLUT1 expression and translocation to the plasma membrane. GLUT1 translocation was associated with a decrease of intracellular ATP by hypoxia. Decreasing ATP levels with antimycin-A and 2-deoxyglucose induced GLUT1 translocation under normoxia. The induction of hypoxia-inducible factor-1α under normoxia did not influence the cell surface expression of GLUT1 or cellular ATP concentration. Interestingly, the translocation of GLUT1 induced by hypoxia was inhibited by the ATP-sensitive potassium (KATP) channel inhibitor glibenclamide, while the mitochondrial KATP channel inhibitor 5-HD did not influence GLUT1 translocation during hypoxia. These observations indicate that a decrease of intracellular ATP triggers GLUT1 translocation to the plasma membrane and is mediated by KATP channels, which would contribute to glucose uptake in HUVECs during hypoxia.
葡萄糖摄取和三磷酸腺苷（ATP）的产生对于内皮细胞的存活和生长很重要。先前的研究表明，缺氧下葡萄糖摄取的增加与葡萄糖转运蛋白（GLUTs）的表达增加有关。然而，GLUT 向细胞表面的转运调节尚未被详细研究。在这里，我们报告了在缺氧条件下内皮细胞中 GLUT1 向质膜易位的特征。将人脐静脉内皮细胞（HUVEC）暴露于 1%O 的缺氧环境 12 小时，这显著诱导了 GLUT1 的表达和向质膜的易位。GLUT1 易位与缺氧引起的细胞内 ATP 减少有关。在常氧条件下，使用抗霉素 A 和 2-脱氧葡萄糖降低 ATP 水平会诱导 GLUT1 易位。常氧下诱导缺氧诱导因子-1α 并不影响 GLUT1 的细胞表面表达或细胞内 ATP 浓度。有趣的是，缺氧诱导的 GLUT1 易位被 ATP 敏感性钾（KATP）通道抑制剂格列本脲抑制，而线粒体 KATP 通道抑制剂 5-HD 则不影响缺氧时 GLUT1 的易位。这些观察结果表明，细胞内 ATP 的减少触发 GLUT1 向质膜的易位，并且由 KATP 通道介导，这将有助于缺氧时 HUVEC 中的葡萄糖摄取。
