Transcriptional Activation Of Hypoxia Sensitive Genes Following Repeated Sprint Exercise In Hypoxia

Abstract

Repeated sprint training in hypoxia (RSTH) utilizes short supramaximal efforts followed by incomplete rest intervals. RSTH has been shown to improve repeated sprint performance compared to repeated sprint training in normoxia. Because of the relatively short exposure to hypoxia compared to live high, train low approaches, the benefits of RSTH have been attributed to local muscular adaptations rather than hypoxia-induced erythropoiesis. Repeated activation of the hypoxia sensitive transcription factors HIF-1α and PGC-1α, and regulation of their gene targets related to angiogenesis (VEGF), mitophagy (BNIP3, PINK1), and glucose metabolism (PDK-M, GLUT4) may underlie these muscular adaptations. PURPOSE: To investigate the transcriptional activation of HIF-1α, PGC-1α and several HIF-1α-target genes following repeated sprint exercise in normoxia and hypoxia. METHODS: Eight recreationally active males (n=8) and one female (n=1) performed 20, 10s all-out sprints in normoxia (1600m) and hypobaric hypoxia (4600m) on a cycle ergometer on two days separated by 2 weeks. Skeletal muscle samples from the vastus lateralis were analyzed for mRNA levels of HIF-1α, PGC-1α, BNIP3, PINK1, VEGF, PDK-M, and GLUT4 pre, post and 3h post exercise in hypoxia and normoxia. Comparisons between condition and time were made using two-way repeated measures ANOVAs. RESULTS: There was a significant increase in mRNA levels for HIF-1α (fold change: 2.6±1.8) and VEGF (fold change: 3.0±1.6) 3h post-exercise in hypoxia (p<.05) but not normoxia. PGC-1α, was higher 3h post-exercise in both hypoxia (fold change: 9.2±4.6) and normoxia (fold change: 6.2±3.8; p<.05). No significant effect of time or group was observed for BNIP3, PINK1, PDK-M, or GLUT4. CONCLUSIONS: Acute sprint exercise in both hypoxia and normoxia induces an increase in the transcription of PGC-1α. However, hypoxia sensitive genes HIF-1α and VEGF were only greater following sprint exercise in hypoxia. Collectively, these findings suggest that sprint exercise stimulates mitochondrial biogenesis, but an additional hypoxic stress is required to induce changes in hypoxia sensitive genes. The downstream effect of these transcriptional activations may increase angiogenesis and mitochondrial signaling in response to RSTH, which may in part explain the benefits of RSTH.