Correlation of Hypoxia Inducible factor-1α and Vascular Endothelium Growth Factor in Rat Myocardium During Aerobic and Anaerobic Exercise (original) (raw)
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Journal of Applied Physiology, 2015
The present study investigated the effects of acute and chronic eccentric exercise on the hypoxia-inducible factor (HIF)-1α activation response and the concomitant modulation of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) expression in rat skeletal muscle. Twenty-four male Wistar rats were randomly assigned to three experimental groups: rested control group, acutely exercised group after an intermittent downhill protocol for 90 min, and acutely exercise group with a previous eccentric training of 8 wk. HIF-1α activation, VEGF and eNOS gene expression, protein content, and promoter activation were assessed in vastus lateralis muscle biopsies. Acute eccentric exercise induced a marked activation of HIF-1α and resulted in increased VEGF and eNOS mRNA level and protein concentration. The binding of HIF-1α to the VEGF and eNOS promoters, measured by a chromatin immunoprecipitation assay, was undetectable in rested rats, whereas it was evident in...
Physiological activation of hypoxia inducible factor-1 in human skeletal muscle
The FASEB Journal, 2005
The human hypoxia inducible factor 1 (HIF-1) system is activated under various pathological conditions, yet less is known about its physiological regulation in healthy human tissue. We have studied the effect of exercise on the activation of HIF-1 in human skeletal muscle. Employing a model where oxygen consumption increases and oxygen tension can be manipulated, nine healthy male subjects performed 45 min of one-legged knee-extension exercise. Biopsies were taken before, directly after, and 30, 120, and 360 min after exercise. Exercise led to elevated HIF-1α protein levels and a more prevalent nuclear staining of HIF-1α. Interestingly, a concurrent decrease in von Hippel-Lindau tumor suppressor protein (VHL) levels was detected in some subjects. Moreover, exercise induced an increase in the DNA binding activity of HIF-1α. Characterization of gene expression by real-time PCR demonstrated that the HIF-1 target genes VEGF and EPO were activated. VEGF mRNA was further increased when blood flow to the exercising leg was restricted. In conclusion, these data clearly demonstrate that physical activity induces the HIF-1-mediated signaling pathway in human skeletal muscle, providing the first evidence that human HIF-1α can be activated during physiologically relevant conditions.
Trends in Medical Research, 2016
During physical activity, oxygen reduction leading to hypoxia affects brain cell metabolisms, induces stabilization of Hypoxia Inducible Factor-1α (HIF-1α) and up-regulate Vesicular Endothelial Growth Factor (VEGF). This study aimed to investigate the correlation of HIF-1α and VEGF of brain tissue in male wistar rat after anaerobic exercise. Twenty four rats were divided into four groups: control, 1x, 3x and 7x in a week of anaerobic exercise. A rat treadmill was used at speed 35 m minG 1 , 20 min for every anaerobic exercise. The HIF-1α and VEGF level were measured by ELISA. The correlation between HIF-1α and VEGF was analyzed using Pearson test. The HIF-1α and VEGF level increased in 1x and 3x a week of anaerobic exercise. The highest HIF-1α and VEGF level were observed in 1x a week of anaerobic exercise. Pearson test between HIF-1α and VEGF showed r = 0.709 and p = 0.000. These findings showed that HIF-1α and VEGF are correlated and anaerobic exercise affects HIF-1α and VEGF level.
Skeletal muscle hypoxia-inducible factor-1 and exercise
Experimental physiology, 2016
Reduced oxygen levels in skeletal muscle during exercise are a consequence of increased oxygen consumption. The cellular response to hypoxia is conferred to a large extent by activation of the hypoxia-sensitive transcription factor hypoxia-inducible factor-1 (HIF-1). The target genes of HIF-1 increase oxygen transport through mechanisms such as erythropoietin-mediated erythropoiesis and vascular endothelial growth factor-induced angiogenesis and improve tissue function during low oxygen availability through increased expression of glucose transporters and glycolytic enzymes, which makes HIF-1 an interesting candidate as a mediator of skeletal muscle adaptation to endurance training. However, HIF-1 may also inhibit cellular oxygen consumption and mitochondrial oxidative metabolism, features discordant with the phenotype of a trained muscle. Skeletal muscle readily adjusts to altered functional demands. Adaptation of skeletal muscle to long-term aerobic training enables better aerobic...
Correlation Between Hypoxia Inducible Factor-1α and Vesicular.pdf
During physical activity, oxygen reduction leading to hypoxia affects brain cell metabolisms, induces stabilization of Hypoxia Inducible Factor-1α (HIF-1α) and up-regulate Vesicular Endothelial Growth Factor (VEGF). This study aimed to investigate the correlation of HIF-1α and VEGF of brain tissue in male wistar rat after anaerobic exercise. Twenty four rats were divided into four groups: control, 1x, 3x and 7x in a week of anaerobic exercise. A rat treadmill was used at speed 35 m minG 1 , 20 min for every anaerobic exercise. The HIF-1α and VEGF level were measured by ELISA. The correlation between HIF-1α and VEGF was analyzed using Pearson test. The HIF-1α and VEGF level increased in 1x and 3x a week of anaerobic exercise. The highest HIF-1α and VEGF level were observed in 1x a week of anaerobic exercise. Pearson test between HIF-1α and VEGF showed r = 0.709 and p = 0.000. These findings showed that HIF-1α and VEGF are correlated and anaerobic exercise affects HIF-1α and VEGF level.
HIF-1α in endurance training: suppression of oxidative metabolism
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2007
During endurance training, exercising skeletal muscle experiences severe and repetitive oxygen stress. The primary transcriptional response factor for acclimation to hypoxic stress is hypoxia-inducible factor-1α (HIF-1α), which upregulates glycolysis and angiogenesis in response to low levels of tissue oxygenation. To examine the role of HIF-1α in endurance training, we have created mice specifically lacking skeletal muscle HIF-1α and subjected them to an endurance training protocol. We found that only wild-type mice improve their oxidative capacity, as measured by the respiratory exchange ratio; surprisingly, we found that HIF-1α null mice have already upregulated this parameter without training. Furthermore, untrained HIF-1α null mice have an increased capillary to fiber ratio and elevated oxidative enzyme activities. These changes correlate with constitutively activated AMP-activated protein kinase in the HIF-1α null muscles. Additionally, HIF-1α null muscles have decreased expre...
Journal of Biological Chemistry, 2000
Hypoxia inducible factor-1 (HIF-1) controls the expression of a number of genes such as Vascular Endothelial Growth Factor (VEGF) and Erythropoeitin in low oxygen conditions (hypoxia). VEGF is strongly induced at both the mRNA and protein expression level by a number of hormones and growth factors in vascular smooth muscle cells (VSMC) independently of the oxygen environment. However, the role of HIF-1α in this induction has not been studied. We report here that HIF-1α protein levels are strongly increased by fetal calf serum in quiescent VSMC. More interestingly, Angiotensin II (Ang II), thrombin, PDGF and other hormones can also increase HIF-1α in VSMC to levels that are substantially more elevated than the hypoxic treatment. HIF-1α induced by Ang II is located in the nucleus, binds to the hypoxic response element and is transcriptionally active. The induction of HIF-1α by hormones is mediated through the production of reactive oxygen species (ROS) since it can be blocked by the ROS inhibitors, diphenyleneiodonium and catalase. Finally, strong induction of VEGF mRNA by Ang II can also be inhibited by these ROS inhibitors. These results implicate HIF-1α and HIF-1-dependent transcriptional activity in the induction of VEGF expression after agonist stimulation and define novel hypoxia-independent mechanisms that should play a major role in vascular remodeling.
European Journal of Applied Physiology, 2009
Intermittent hypoxic exposure with exercise training is based on the assumption that brief exposure to hypoxia is suYcient to induce beneWcial muscular adaptations mediated via hypoxia-inducible transcription factors (HIF). We previously demonstrated (Mounier et al. Med Sci Sports Exerc 38:1410-1417) that leukocytes respond to hypoxia with a marked inter-individual variability in HIF-1 mRNA. This study compared the eVects of 3 weeks of intermittent hypoxic training on hif gene expression in both skeletal muscle and leukocytes. Male endurance athletes (n = 19) were divided into an Intermittent Hypoxic Exposure group (IHE) and a Normoxic Training group (NT) with each group following a similar 3-week exercise training program. After training, the amount of HIF-1 mRNA in muscle decreased only in IHE group (¡24.7%, P < 0.05) whereas it remained unchanged in leukocytes in both groups. The levels of vEGF 121 and vEGF 165 mRNA in skeletal muscle increased signiWcantly after training only in the NT group (+82.5%, P < 0.05 for vEGF 121 ; +41.2%, P < 0.05 for vEGF 165 ). In leukocytes, only the IHE group showed a signiWcant change in vEGF 165 (¡28.2%, P < 0.05). The signiWcant decrease in HIF-1 mRNA in skeletal muscle after hypoxic training suggests that transcriptional and post-transcriptional regulations of the hif-1 gene are diVerent in muscle and leukocytes.
The Effect of Physical Activity on VEGF and HIF-1 Signaling
Journal of Clinical Research in Paramedical Sciences, 2020
Context: The purpose of the present study was to investigate the context of research into the physiological roles of VEGF and the most important potential mechanisms that may lead to a temporary decrease in serum VEGF, as well as to perform a desirable conclusion and provide more relevant data from previous research. Methods: In this study, articles were searched in specialized databases and 40 related articles were selected based on inclusion and exclusion criteria. Then the effect of physical activity on VEGF and HIF-1 signaling was investigated. Results: Exercise and physical activity by stimulating and activating VEGF and HIF-1 signals may induce generating new arteries and angiogenesis. Conclusions: The present study showed that physical activity increases capillary density by increasing the level of diffusion, increasing the time of exchange between blood and tissue, and decreasing the oxygen diffusion distance. As a result, capillary dilatation and capacity increase and ultim...