Effect of exercise on HIF-1 and VEGF signaling
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概要
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This review summarizes the literature describing the significance of various conditions, such as hypoxia, oxidative stress, and, above all, physical exercise, in the hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) signaling pathway mainly in skeletal muscle. HIF-1α acts as a master regulator for the expression of genes involved in the hypoxia response of most mammalian cells. Namely, HIF-1α initiates transcription of various hypoxia-adaptive genes, such as angiogenesis, glycolysis, and erythropoiesis, after the formation of heterodimer with HIF-1β. Among them, VEGF is the most potent endothelial specific mitogen, which recruits endothelial cells into hypoxic foci and avascular area and stimulates their proliferation. The study on acute exercise shows that several components of the HIF-1 pathway, involving VEGF and erythropoietin, are activated in response to acute changes in oxygen demand in human skeletal muscle, suggesting that oxygen sensitive pathways could be relevant for adaptaion to physical activity by increasing capillary growth. Also, the effects of endurance training on the activity of the HIF pathway in human skeletal muscle under hypoxic conditions appear to be definitely higher than those under normoxic conditions, indicating that combining hypoxia with exercise training appears to improve some aspects of muscle O2 transport and/or metabolism. On the other hand, increased levels of reactive oxygen species (ROS) due to physical exercise induce the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), which regulates mitochondrial biogenesis in multiple cell types, resulting in increases in VEGF expression and subsequent angiogenesis, strongly suggesting HIF-1α-independent regulation of VEGF and angiogenesis. Thus, the precise relationship among exercise, the HIF-1 pathway including VEGF, PGC-1α, and ROS needs further study.
著者
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OGASAWARA Junetsu
Department of Kinesiology, Graduate School of Science, Tokyo Metropolitan University
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Shirato Ken
Laboratory Of Physiological Sciences Faculty Of Human Sciences Waseda University
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Imaizumi Kazuhiko
Laboratory Of Physiological Sciences Faculty Of Human Sciences Waseda University
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Ohno Hideki
Department Of Gastroenterology Graduate School Of Medicine University Of Tokyo
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Ishida Hitoshi
Third Department Of Internal Medicine Kyorin University School Of Medicine
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Kizaki Takako
Department Of Molecular Predictive Medicine And Sport Science Kyorin University School Of Medicine
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Sakurai Takuya
Department of Electrical and Electronic Engineering, Faculty of Engineering, Shinshu University, 4-17-1 Wakasato, Nagano 380-8553, Japan
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Sato Shogo
Department of Molecular Predictive Medicine and Sport Science, Kyorin University, School of Medicine
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Sumitani Yoshikazu
Department of Molecular Predictive Medicine and Sport Science, Kyorin University, School of Medicine
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OHNO Hideki
Department of Gastroenterology and Cancer Gene Regulation, Kanazawa University Graduate School of Medical Sciences
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