Tang Kechun, Breen Ellen C, Wagner Harrieth, Brutsaert Tom D, Gassmann Max, Wagner Peter D
Division of Physiology (0623A), Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Respir Physiol Neurobiol. 2004 Nov 30;144(1):71-80. doi: 10.1016/j.resp.2004.04.009.
To determine if hypoxia-inducible factor-1 (HIF-1) may regulate skeletal muscle vascular endothelial growth factor (VEGF) expression in response to exercise or hypoxia, rats underwent 1h sciatic nerve electrical stimulation (ES), hypoxic exposure (H) or combined stimuli. HIF-1alpha protein levels increased six-fold with maximal (8V) ES with or without H. Similar HIF-1alpha increases occurred with sub-maximal (6V and 4V) ES plus H, but not in sub-maximal ES or H alone. VEGF mRNA and protein levels increased three-fold in sub-maximal ES or H alone, six-fold in sub-maximal ES plus H, 6.3-fold with maximal ES, and 6.5-fold after maximal ES plus H. These data suggest: (1) intracellular hypoxia during normoxic exercise may exceed that during 8% oxygen breathing at rest and is more effective in stimulating HIF-1alpha; (2) HIF-1 may be an important regulator of exercise-induced VEGF transcription; and (3) breathing 8% O(2) does not alter HIF-1alpha expression in skeletal muscle, implying that exercise-generated signals contribute to the regulation of HIF-1alpha and/or VEGF.
为了确定缺氧诱导因子-1（HIF-1）是否可能响应运动或缺氧来调节骨骼肌血管内皮生长因子（VEGF）的表达，对大鼠进行了1小时的坐骨神经电刺激（ES）、低氧暴露（H）或联合刺激。无论有无低氧暴露，最大强度（8V）电刺激时HIF-1α蛋白水平增加了6倍。亚最大强度（6V和4V）电刺激加低氧暴露时HIF-1α也有类似增加，但单独亚最大强度电刺激或单独低氧暴露时则没有。单独亚最大强度电刺激或单独低氧暴露时VEGF mRNA和蛋白水平增加3倍，亚最大强度电刺激加低氧暴露时增加6倍，最大强度电刺激时增加6.3倍，最大强度电刺激加低氧暴露后增加6.5倍。这些数据表明：（1）常氧运动期间的细胞内缺氧可能超过静息时8%氧气呼吸期间的缺氧，并且在刺激HIF-1α方面更有效；（2）HIF-1可能是运动诱导的VEGF转录的重要调节因子；（3）呼吸8% O₂不会改变骨骼肌中HIF-1α的表达，这意味着运动产生的信号有助于调节HIF-1α和/或VEGF。
