School of Biomedical Sciences, University of Plymouth, Plymouth, United Kingdom.
PLoS One. 2022 Aug 8;17(8):e0266905. doi: 10.1371/journal.pone.0266905. eCollection 2022.
Dietary nitrate lowers the oxygen cost of human exercise. This effect has been suggested to result from stimulation of coupling efficiency of skeletal muscle oxidative phosphorylation by reduced nitrate derivatives. In this paper, we report the acute effects of sodium nitrite on the bioenergetic behaviour of cultured rat (L6) myocytes. At odds with improved efficiency of mitochondrial ATP synthesis, extracellular flux analysis reveals that a ½-hour exposure to NaNO2 (0.1-5 μM) does not affect mitochondrial coupling efficiency in static myoblasts or in spontaneously contracting myotubes. Unexpectedly, NaNO2 stimulates the rate of glycolytic ATP production in both myoblasts and myotubes. Increased ATP supply through glycolysis does not emerge at the expense of oxidative phosphorylation, which means that NaNO2 acutely increases the rate of overall myocellular ATP synthesis, significantly so in myoblasts and tending towards significance in contractile myotubes. Notably, NaNO2 exposure shifts myocytes to a more glycolytic bioenergetic phenotype. Mitochondrial oxygen consumption does not decrease after NaNO2 exposure, and non-mitochondrial respiration tends to drop. When total ATP synthesis rates are expressed in relation to total cellular oxygen consumption rates, it thus transpires that NaNO2 lowers the oxygen cost of ATP supply in cultured L6 myocytes.
饮食中的硝酸盐可降低人体运动的氧气消耗。这种效应被认为是由于还原的硝酸盐衍生物刺激了骨骼肌氧化磷酸化的偶联效率。在本文中，我们报告了亚硝酸钠对培养的大鼠（L6）成肌细胞生物能行为的急性影响。与线粒体 ATP 合成效率的提高相反，细胞外通量分析表明，在静息成肌细胞或自发收缩的肌管中，暴露于亚硝酸钠（0.1-5 μM）半小时不会影响线粒体偶联效率。出人意料的是，亚硝酸钠刺激了成肌细胞和肌管中糖酵解 ATP 生成的速率。通过糖酵解增加的 ATP 供应并非以氧化磷酸化为代价，这意味着亚硝酸钠急性增加了整体肌细胞的 ATP 合成速率，在成肌细胞中尤为明显，在收缩肌管中也有趋于显著的趋势。值得注意的是，亚硝酸钠暴露会使细胞向更具糖酵解生物能表型转变。亚硝酸钠暴露后线粒体耗氧量不会降低，而非线粒体呼吸趋于下降。当总 ATP 合成速率与总细胞耗氧量相关表达时，结果表明亚硝酸钠降低了培养的 L6 成肌细胞中 ATP 供应的氧气消耗成本。
