Department of Anatomy and Neurobiology, Biomedical Science Institute, Kyung Hee University, Seoul, Republic of Korea.
Cancer Lett. 2010 Sep 28;295(2):236-41. doi: 10.1016/j.canlet.2010.03.006. Epub 2010 Mar 24.
Ethyl pyruvate is a simple derivative of the endogenous metabolite pyruvate. Pyruvate is the starting substrate for the tricarboxylic acid (TCA) cycle and plays a central role in intermediary metabolism. The present study was to determine whether ethyl pyruvate affects the expression of hypoxia-inducible factor 1 alpha (HIF-1alpha) and to explore the mechanism of HIF-1alpha regulation. We found that ethyl pyruvate increased HIF-1alpha stability via inhibition of pVHL-mediated degradation. Furthermore, ethyl pyruvate enhanced the reactive oxygen species (ROS) generated through the TCA cycle in mitochondria. Taken together, our results support a novel role for ethyl pyruvate in HIF-1alpha stabilization by which high rates of the TCA cycle can promote ROS production.
丙酮酸乙酯是内源性代谢物丙酮酸的简单衍生物。丙酮酸是三羧酸 (TCA) 循环的起始底物，在中间代谢中起核心作用。本研究旨在确定丙酮酸乙酯是否影响缺氧诱导因子 1α（HIF-1α）的表达，并探讨 HIF-1α 调节的机制。我们发现，丙酮酸乙酯通过抑制 pVHL 介导的降解来增加 HIF-1α 的稳定性。此外，丙酮酸乙酯增强了线粒体 TCA 循环中产生的活性氧 (ROS)。总之，我们的结果支持丙酮酸乙酯通过促进 TCA 循环来稳定 HIF-1α 的新作用，从而促进 ROS 的产生。
