Division of Physiology, Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0623, USA.
Respir Physiol Neurobiol. 2010 Jan 31;170(1):16-22. doi: 10.1016/j.resp.2009.10.007. Epub 2009 Oct 21.
Muscle VEGF expression is upregulated by exercise. Whether this VEGF response is regulated by transcription and/or post-transcriptional mechanisms is unknown. Hypoxia may be responsible: myocyte P(O2) falls greatly during exercise and VEGF is a hypoxia-responsive gene. Whether exercise induces VEGF expression in other organs important to acute physical activity is also unknown. To address these questions, we created a VEGF-Luciferase reporter mouse and measured VEGF transcription, mRNA and protein responses to (a) acute exercise and (b) short-term hypoxia (FI(O2) = 0.06) in brain (brainstem, cerebellum, cortex, hippocampus and striatum), muscle, lung, heart and liver. Exercise increased VEGF transcription, mRNA and protein in brain (hippocampus only), lungs and skeletal muscles, but not liver or heart. Hypoxia increased VEGF expression only in brain (cortex, hippocampus and striatum). New transcription appears to be a major exercise-induced regulatory step for increasing VEGF expression in muscle, lung and brain. Hippocampal VEGF expression was the only component of the exercise response recapitulated by hypoxia equivalent to the Everest summit.
肌肉中的血管内皮生长因子表达受运动调控。目前尚不清楚这种血管内皮生长因子的反应是受转录和/或转录后机制调控的。缺氧可能是原因之一：运动期间心肌的氧分压会大幅下降，而血管内皮生长因子是一种对缺氧有反应的基因。运动是否会引起对急性体力活动很重要的其他器官中的血管内皮生长因子表达，目前也尚不清楚。为了解决这些问题，我们构建了一种血管内皮生长因子-荧光素酶报告基因小鼠，并测量了血管内皮生长因子的转录、mRNA 和蛋白对（a）急性运动和（b）短期缺氧（FI（O2）= 0.06）的反应，在脑（脑干、小脑、皮质、海马和纹状体）、肌肉、肺、心脏和肝脏中。运动增加了脑（仅海马）、肺和骨骼肌中的血管内皮生长因子转录、mRNA 和蛋白，但对肝脏或心脏没有影响。缺氧仅增加了脑（皮质、海马和纹状体）中的血管内皮生长因子表达。新的转录似乎是运动诱导肌肉、肺和脑中血管内皮生长因子表达增加的主要调节步骤。海马中的血管内皮生长因子表达是缺氧模拟珠穆朗玛峰效应的唯一组成部分，重现了运动反应。
