Stem Cells, Ageing and Molecular Physiology Research (SCAMP) Unit, Exercise Metabolism and Adaptation Research Group (EMARG), Research Institute for Sport and Exercise Sciences (RISES), Liverpool John Moores University, Liverpool, UK.
Department of Internal Medicine, Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, IA, 52246, USA.
Mol Cell Biochem. 2018 Jul;444(1-2):109-123. doi: 10.1007/s11010-017-3236-1. Epub 2017 Nov 30.
Glucose restriction (GR) impairs muscle cell differentiation and evokes myotube atrophy. Resveratrol treatment in skeletal muscle cells improves inflammatory-induced reductions in skeletal muscle cell differentiation. We therefore hypothesised that resveratrol treatment would improve muscle cell differentiation and myotube hypertrophy in differentiating C2C12 myoblasts and mature myotubes during GR. Glucose restriction at 0.6 g/L (3.3 mM) blocked differentiation and myotube hypertrophy versus high-glucose (4.5 g/L or 25 mM) differentiation media (DM) conditions universally used for myoblast culture. Resveratrol (10 µM) treatment increased SIRT1 phosphorylation in DM conditions, yet did not improve differentiation when administered to differentiating myoblasts in GR conditions. Resveratrol did evoke increases in hypertrophy of mature myotubes under DM conditions with corresponding elevated Igf-I and Myhc7 gene expression, coding for the 'slow' type I MYHC protein isoform. Inhibition of SIRT1 via EX-527 administration (100 nM) also reduced myotube diameter and area in DM conditions and resulted in lower gene expression of Myhc 1, 2 and 4 coding for 'intermediate' and 'faster' IIx, IIa and IIb protein isoforms, respectively. Resveratrol treatment did not appear to modulate phosphorylation of energy-sensing protein AMPK or protein translation initiator P70S6K. Importantly, in mature myotubes, resveratrol treatment was able to ameliorate reduced myotube growth in GR conditions over an acute 24-h period, but not over 48-72 h. Overall, resveratrol evoked myotube hypertrophy in DM conditions while favouring 'slower' Myhc gene expression and acutely ameliorated impaired myotube growth observed during glucose restriction.
葡萄糖限制（GR）会损害肌肉细胞分化并引发肌管萎缩。在骨骼肌细胞中，白藜芦醇的治疗可以改善炎症引起的骨骼肌细胞分化减少。因此，我们假设在 GR 期间，白藜芦醇处理会改善分化中的 C2C12 成肌细胞和成熟肌管中的肌肉细胞分化和肌管肥大。与普遍用于成肌细胞培养的高葡萄糖（4.5g/L 或 25mM）分化培养基（DM）条件相比，0.6g/L（3.3mM）的葡萄糖限制会阻止分化和肌管肥大。白藜芦醇（10μM）处理在 DM 条件下增加了 SIRT1 的磷酸化，但在 GR 条件下给予分化中的成肌细胞时，并未改善分化。白藜芦醇在 DM 条件下确实会引起成熟肌管的肥大增加，同时伴随着 IGF-I 和 Myhc7 基因表达的升高，该基因编码“慢”型 I 型 MYHC 蛋白同工型。通过 EX-527 给药抑制 SIRT1（100nM）也会降低 DM 条件下的肌管直径和面积，并导致编码“中间”和“更快”的 IIx、IIa 和 IIb 蛋白同工型的 Myhc1、2 和 4 的基因表达降低。白藜芦醇处理似乎不会调节能量感应蛋白 AMPK 的磷酸化或蛋白质翻译起始因子 P70S6K。重要的是，在成熟的肌管中，白藜芦醇处理能够在急性 24 小时内改善 GR 条件下减少的肌管生长，但不能在 48-72 小时内改善。总的来说，白藜芦醇在 DM 条件下引起肌管肥大，同时有利于“较慢”的 Myhc 基因表达，并在葡萄糖限制期间急性改善受损的肌管生长。
