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http://hdl.handle.net/11375/22155
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DC Field | Value | Language |
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dc.contributor.advisor | McClelland, Grant | - |
dc.contributor.author | Brooks, Taylor | - |
dc.date.accessioned | 2017-10-12T12:06:36Z | - |
dc.date.available | 2017-10-12T12:06:36Z | - |
dc.date.issued | 2017 | - |
dc.identifier.uri | http://hdl.handle.net/11375/22155 | - |
dc.description.abstract | For decades researchers have observed a reduction in exercise-induced blood lactate accumulation transitioning from acute to chronic hypoxia (the ‘lactate paradox’). Hypoxia inducible factor (HIF1-α) has been hypothesized to direct these metabolic changes during hypoxia through the induction of pyruvate dehydrogenase kinase 1 (PDK1). Activation of PDK1 inhibits aerobic glucose metabolism through pyruvate dehydrogenase, and promotes lactate production. Previous work in our lab revealed HIF1-α and PDK1 protein expression correlates to changes in lactate production with the transition from acute to chronic hypoxia in CD-1 mice, revealing a putative mechanism explaining the paradoxical reduction in lactate. We exposed differentiated C2C12 cells to 1% O2 for 4h, 24h, 96h and compared them to time-matched controls in 21% O2. In addition, we used 1 mM of the HIF-agonist DMOG at 20.95% O2 and 25 µM of the HIF antagonist PX-478 in 1% O2. We found that C2C12 myotubes decreased the rate of lactate accumulation and release with long-term hypoxia, similar to observations in vivo. This also corresponds to changes in LDH enzyme activity and PDK1 protein expression. However, DMOG-induced PDK1 expression does not match changes in lactate accumulation. Our findings confirm the existence of the lactate paradox at the cellular level and suggest a role for HIF signaling in the decline of lactate with chronic hypoxia. | en_US |
dc.language.iso | en | en_US |
dc.title | INFLUENCE OF THE TRANSITION FROM ACUTE TO CHRONIC HYPOXIA ON PYRUVATE DEHYDROGENASE KINASE 1 AND LACTATE ACCUMULATION IN C2C12 CELLS | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Biology | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science (MSc) | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Brooks_Taylor_M_201709_MSc.docx | Environmental Physiology | 763.34 kB | Microsoft Word XML | View/Open |
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