Stange Katja, Schumacher Toni, Miersch Claudia, Whelan Rose, Klünemann Martina, Röntgen Monika
Institute of Muscle Biology and Growth, Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.
Nutritional Physiology and Dietetics, International University of Applied Sciences (IU), Juri-Gagarin-Ring 152, 99084 Erfurt, Germany.
Curr Issues Mol Biol. 2023 Mar 23;45(4):2661-2680. doi: 10.3390/cimb45040174.
An optimal supply of L-methionine (L-Met) improves muscle growth, whereas over-supplementation exerts adverse effects. To understand the underlying mechanisms, this study aims at exploring effects on the growth, viability, ROS production, and mitochondrial bioenergetics of C2C12 (mouse) and QM7 (quail) myoblasts additionally supplemented (100 or 1000 µM) with L-Met, DL-methionine (DL-Met), or DL-2-hydroxy-4-(methylthio)butanoic acid (DL-HMTBA). In both cell lines, all the supplements stimulated cell growth. However, in contrast to DL-Met, 1000 µM of L-Met (C2C12 cells only) or DL-HMTBA started to retard growth. This negative effect was stronger with DL-HMTBA and was accompanied by significantly elevated levels of extracellular HO, an indicator for OS, in both cell types. In addition, oversupplementation with DL-HMTBA (1000 µM) induced adaptive responses in mitochondrial bioenergetics, including reductions in basal (C2C12 and QM7) and ATP-synthase-linked (C2C12) oxygen consumption, maximal respiration rate, and reserve capacity (QM7). Only QM7 cells switched to nonmitochondrial aerobic glycolysis to reduce ROS production. In conclusion, we found a general negative effect of methionine oversupplementation on cell proliferation. However, only DL-HMTBA-induced growth retardation was associated with OS and adaptive, species-specific alterations in mitochondrial functionality. OS could be better compensated by quail cells, highlighting the role of species differences in the ability to cope with methionine oversupplementation.
最佳的L-蛋氨酸（L-Met）供应可促进肌肉生长，而过量补充则会产生不利影响。为了解其潜在机制，本研究旨在探讨额外补充（100或1000μM）L-蛋氨酸、DL-蛋氨酸（DL-Met）或DL-2-羟基-4-（甲硫基）丁酸（DL-HMTBA）对C2C12（小鼠）和QM7（鹌鹑）成肌细胞的生长、活力、活性氧（ROS）产生以及线粒体生物能量学的影响。在这两种细胞系中，所有补充剂均刺激细胞生长。然而，与DL-Met不同，1000μM的L-Met（仅C2C12细胞）或DL-HMTBA开始阻碍生长。DL-HMTBA的这种负面影响更强，并且在两种细胞类型中均伴随着细胞外HO水平的显著升高，HO是氧化应激（OS）的一个指标。此外，过量补充DL-HMTBA（1000μM）会诱导线粒体生物能量学的适应性反应，包括基础（C2C12和QM7）和ATP合酶相关（C2C12）的氧气消耗、最大呼吸速率以及储备能力（QM7）的降低。只有QM7细胞转向非线粒体有氧糖酵解以减少ROS产生。总之，我们发现蛋氨酸过量补充对细胞增殖具有普遍的负面影响。然而，只有DL-HMTBA诱导的生长迟缓与OS以及线粒体功能的适应性、物种特异性改变有关。鹌鹑细胞对OS的补偿能力更强，这突出了物种差异在应对蛋氨酸过量补充能力方面的作用。
