Master of Science
Dr. James F. Staples and Dr. Timothy R.H. Regnault
Using the C2C12 mouse muscle myoblast cell line, I sought to investigate the hypothesis that differentiation under hypoxia impairs muscle mitochondrial respiratory function irreversibly. Resveratrol (RSV) will increase expression of markers of mitochondrial biogenesis and reverse the hypoxia-induced depression of O2 consumption rates. Hypoxia decreased oxygen consumption rates after five days of differentiation and after two days of normoxic recovery. This coincided with a hypoxia-induced decrease in protein levels of the NDUFB8 subunit of complex I of the electron transport chain and decreases in mRNA levels of mitochondrial biogenesis transcription factors, both of which could contribute to the alterations observed in oxygen consumption rates. Normoxic recovery supplemented with RSV did increase oxygen consumption rates, however this increase was not observed across all oxygen concentrations that were measured which may have be associated with the decreases in cell viability observed with RSV treatment. RSV also increased mitochondrial abundance which could account for the increases in oxygen consumption rate. RSV did increase some skeletal muscle markers of mitochondrial biogenesis, but did not increase protein levels of the subunit NDUFB8 of complex I. Hypoxia alters mitochondrial biogenesis and skeletal muscle respiratory function and may induce permanent changes in mitochondrial respiration of differentiating skeletal muscle cells. RSV treatment did not consistently reverse hypoxic alterations during normoxic recovery and negatively impacted cell viability indicating that RSV may not be a suitable pharmacological intervention for skeletal muscle cells which have differentiated under hypoxia.
Belgrave, Kathleen R., "Hypoxia-Induced Alterations in Skeletal Muscle Cell Respiration and Resveratrol as a Potential Pharmacological Intervention" (2012). University of Western Ontario - Electronic Thesis and Dissertation Repository. Paper 659.