After
myocardial ischemia-reperfusion,
fatty acid oxidation shows fast recovery while
glucose oxidation rates remain depressed. A metabolic shift aimed at increasing
glucose oxidation has shown to be beneficial in models of
myocardial ischemia-reperfusion. However, strategies aimed at increasing
glucose consumption in the clinic have provided mixed results and have not yet reached routine clinical practice. A better understanding of the mechanisms underlying the protection afforded by increased
glucose oxidation may facilitate the transfer to the clinic. The purpose of this study was to evaluate if the modulation of
reactive oxygen species (ROS) was involved in the protection afforded by increased
glucose oxidation. Firstly, we characterized an H9C2 cellular model in which the use of
glucose or
galactose as substrates can modulate glycolysis and oxidative phosphorylation pathways. In this model, there were no differences in morphology, cell number, or
ATP and PCr levels. However,
galactose-grown cells consumed more
oxygen and had an increased Krebs cycle turnover, while cells grown in
glucose had increased aerobic glycolysis rate as demonstrated by higher
lactate and
alanine production. Increased aerobic glycolysis was associated with reduced ROS levels and protected the cells against simulated
ischemia-reperfusion injury. Furthermore, ROS scavenger N-acetyl
cysteine (NAC) was able to reduce the amount of ROS and to prevent cell death. Lastly, cells grown in
galactose showed higher activation of mTOR/Akt signaling pathways. In conclusion, our results provide evidence indicating that metabolic shift towards increased glycolysis reduces mitochondrial ROS production and prevents cell death during
ischemia-reperfusion injury.