The Effects of Acute and Chronic Hypoxia on Muscle Metabolism in Mice

Abstract

<p>Under hypoxia mammals face many challenges, especially in terms of energy production. To conserve O2, mammals may enter a hypometabolic state or rely more heavily on anaerobic metabolism. However, the latter strategy is not a viable option during chronic hypoxia and other cellular changes are needed. Under chronic hypoxia, mammals have been predicted to alter their metabolic machinery in an attempt to increase the efficiency of ATP production to reduce the amount of O2 used by the mitochondria. One way efficiency is believed to increase is through a change in the composition of cytochrome c oxidase (COX). Cell culture experiments have shown a decrease in the COX4-1 isoform and an increase in the COX4-2 isoform under hypoxia, leading to an increase in the reaction efficiency of COX. In the present study, I observed an increase in the mRNA levels of COX4-2 after 24hrs of hypoxia. However, this change was not mirrored by corresponding changes at the protein level. Further, I examined the phosphorylation state of pyruvate dehydrogenase (PDH) as an indicator of PDH activity. Under chronic hypoxia resting mice exhibited a significant rise in PDH phosphorylation. This increase may represent a decrease in PDH activity and a decreased reliance on carbohydrate derived acetyl-CoA.</p> <p>I also explored the effects plastic changes in muscle during chronic hypoxia had on muscle metabolism during acute exercise. In hypoxic post-exercise mice, a significant increase in muscle lactate levels was observed compared to rest. This rise was not present in control mice, suggesting that acclimated mice were relying more heavily on anaerobic metabolism. However, there were no significant changes in PDH phosphorylation in post-exercise mice which could help to explain elevated muscle lactate levels.</p>