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.

中文翻译：

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增强糖酵解可减少ROS的产生，从而防止缺血再灌注损伤。

心肌缺血-再灌注后，脂肪酸氧化显示快速恢复，而葡萄糖氧化速率仍然降低。在心肌缺血-再灌注模型中，旨在增加葡萄糖氧化的代谢转移已显示是有益的。然而，旨在增加临床中葡萄糖消耗的策略已经提供了混合的结果，还没有达到常规的临床实践。对增加的葡萄糖氧化所提供的保护机制的更好理解可能有助于转移至临床。这项研究的目的是评估是否通过增加葡萄糖氧化来提供活性氧（ROS）的调节。首先，我们表征了一个H9C2细胞模型，其中使用葡萄糖或半乳糖作为底物可以调节糖酵解和氧化磷酸化途径。在此模型中，形态，细胞数量或ATP和PCr水平没有差异。然而，半乳糖生长的细胞消耗更多的氧气，并增加了Krebs循环，而葡萄糖中生长的细胞则有氧糖酵解速率增加，这可以通过较高的乳酸和丙氨酸产生来证明。有氧糖酵解增加与ROS水平降低有关，并保护细胞免受模拟的缺血再灌注损伤。此外，ROS清除剂N-乙酰半胱氨酸（NAC）能够减少ROS的量并防止细胞死亡。最后，在半乳糖中生长的细胞显示出mTOR / Akt信号通路的更高激活。结论，