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Hypoxia 2009 Speakers
Randy Johnson
Molecular Biology Section, Division of Biological Sciences, UC San Diego San Diego, CA 92130
Email: rjohnson@biomail.ucsd.edu
Talk Title: Exercise performance in mice lacking HIF-1 in the skeletal muscle
Session: The Working Skeletal Muscle
Abstract: During endurance training, exercising skeletal muscle experiences severe and repetitive oxygen stress, and the muscle’s ability to cope with and improve its function through that stress is central to its role in the body. The primary transcriptional response factor for hypoxic adaptation is hypoxia inducible factor-1a (HIF-1a), which upregulates glycolysis and angiogenesis in response to low levels of tissue oxygenation. To examine the role of HIF-1a in endurance training, we have created mice specifically lacking skeletal muscle HIF-1a 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-1a null mice have already upregulated this parameter without training. Furthermore, untrained HIF-1a 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-1a null muscles. Additionally, HIF-1a null muscles have decreased expression of pyruvate dehydrogenase kinase I, a HIF-1a target that inhibits oxidative metabolism. This data demonstrates that removal of HIF-1a causes an adaptive response in skeletal muscle akin to endurance training, and provides evidence for the suppression of mitochondrial biogenesis by HIF-1a in normal tissue.

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