Hypoxia induces the translocation of glucose transporter 1 to the plasma membrane in vascular endothelial cells
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The Journal of Physiological Sciences Open Access
ORIGINAL PAPER
Hypoxia induces the translocation of glucose transporter 1 to the plasma membrane in vascular endothelial cells Abdullah Al Mamun1,2, Hisaki Hayashi1, Aya Yamamura1, Md Junayed Nayeem1 and Motohiko Sato1*
Abstract 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 2) 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. Keywords: Glucose transporters, Hypoxia, Endothelial cells, ATP, ATP-sensitive potassium channel Introduction Glucose is the essential source of energy for most cells. Glucose and other carbohydrates are transported from the surrounding fluid into cells by a family of membrane integral proteins called glucose transporters (GLUTs) [1]. To date, 14 GLUTs have been identified in humans, with GLUT1, GLUT3, and GLUT4 being the most commonly expressed in a wide variety of cells [1, 2]. Physiological stimuli induce GLUT expression to facilitate the incorporation of an appropriate quantity of glucose for energy production. For example, hypoxia stimulates glucose transport into cells by increasing the expression of *Correspondence: motosato@aichi‑med‑u.ac.jp 1 Department of Physiology, Aichi Medical University, 1‑1 Yazako‑Karimata, Nagakute‑City, Aichi 4801165, Japan Full list of author information is available at the end of the article
GLUT1 [3, 4]. These processes are regulated to maintain homeostasis, and abnormal expression of GLUTs is often associated with human diseases [2]. The elevated expression of GLUT1 and/or GLUT3 is associated with poor survival in many solid cancers, including gastric cancer [5], breast cancer [6], lung cancer [7], and glioblastoma [8]. In addition, the cell surface localizatio
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