Wei Zeng1, Zeting Xing1, Meiyun Tan1, Yanwen Wu1, Chunyuan Zhang2. 1. Department of Anesthesiology, Affiliated Boai Hospital of Zhongshan, Southern Medical University, Guangdong, 528400, China. 2. Department of Anesthesiology, Affiliated Boai Hospital of Zhongshan, Southern Medical University, Guangdong, 528400, China. Zhangchunyuan88888@163.com.
Abstract
OBJECTIVE: Activated macrophages undergo a metabolic shift from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, which plays a critical role in inflammation. Increasing evidence suggests the important role of propofol in the regulation of inflammatory response and metabolism, but the effect of propofol on the metabolic shift in macrophage, and the mechanisms involved remain unclear. METHODS: The effect of propofol on the metabolic switch was analyzed by extracellular acidification rate and oxygen consumption rate assays. The effect of propofol on glycolysis was analyzed by lactate and glucose uptake assay. The mRNA, protein, cell surface levels of glucose transporter 1 (GLUT1) and the silencing of GLUT1 were employed to understand the effects of GLUT1-mediated metabolism by propofol. Finally, to understand the antioxidation of propofol on the regulation of metabolism, the reactive oxygen species (ROS) production and NADPH activity were performed. RESULTS: We show that propofol can change the metabolic pathway switch from aerobic glycolysis to OXPHOS in LPS-activated macrophages. Moreover, propofol suppresses aerobic glycolysis via inhibited GLUT1-mediated glucose uptake. Furthermore, we show that propofol reduces ROS overproduction, which in turn inhibits GLUT1 expression. Finally, we find that propofol reduces ROS production via inhibits NADPH activity. CONCLUSION: These findings shed light on the function and mechanism of propofol in the metabolic switch and highlight the importance of targeting metabolism by propofol in the clinical medication of inflammatory diseases.
OBJECTIVE: Activated macrophages undergo a metabolic shift from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, which plays a critical role in inflammation. Increasing evidence suggests the important role of propofol in the regulation of inflammatory response and metabolism, but the effect of propofol on the metabolic shift in macrophage, and the mechanisms involved remain unclear. METHODS: The effect of propofol on the metabolic switch was analyzed by extracellular acidification rate and oxygen consumption rate assays. The effect of propofol on glycolysis was analyzed by lactate and glucose uptake assay. The mRNA, protein, cell surface levels of glucose transporter 1 (GLUT1) and the silencing of GLUT1 were employed to understand the effects of GLUT1-mediated metabolism by propofol. Finally, to understand the antioxidation of propofol on the regulation of metabolism, the reactive oxygen species (ROS) production and NADPH activity were performed. RESULTS: We show that propofol can change the metabolic pathway switch from aerobic glycolysis to OXPHOS in LPS-activated macrophages. Moreover, propofol suppresses aerobic glycolysis via inhibited GLUT1-mediated glucose uptake. Furthermore, we show that propofol reduces ROS overproduction, which in turn inhibits GLUT1 expression. Finally, we find that propofol reduces ROS production via inhibits NADPH activity. CONCLUSION: These findings shed light on the function and mechanism of propofol in the metabolic switch and highlight the importance of targeting metabolism by propofol in the clinical medication of inflammatory diseases.