Cobalt chloride can create hypoxia-like state in vitro (referred to as chemical hypoxia). Several studies have suggested that chemical hypoxia may cause deleterious effects on myogenesis. The intrinsic underlying mechanisms of myoblast differentiation, however, are not fully understood. Here, we show that cobalt chloride strongly suppresses myoblast differentiation in a dose-dependent manner. The impaired myoblast differentiation is accompanied by downregulation of myogenic regulatory factor myogenin. Under chemical hypoxia, myogenin stability is decreased at mRNA and protein levels. A muscle-specific E3 ubiquitin ligase MAFbx, which can target myogenin protein for proteasomal degradation, is upregulated along with changes in Akt/Foxo and AMPK/Foxo signaling pathways. A proteasome inhibitor completely prevents cobalt chloride-mediated decrease in myogenin protein. These results suggest that cobalt chloride might modulate myogenin expression at post-transcriptional and post-translational levels, resulting in the failure of the myoblasts to differentiate into myotubes.

氯化钴可以在体外产生类似缺氧的状态（称为化学性缺氧）。几项研究表明，化学性缺氧可能对肌生成造成有害影响。然而，成肌细胞分化的内在潜在机制尚不完全清楚。在这里，我们表明氯化钴以剂量依赖的方式强烈抑制成肌细胞的分化。成肌细胞分化受损伴随着成肌调节因子肌成素的下调。在化学性缺氧条件下，肌生成素的稳定性在mRNA和蛋白质水平降低。肌肉特异性E3泛素连接酶MAFbx可以靶向肌生成素蛋白进行蛋白酶体降解，并随着Akt / Foxo和AMPK / Foxo信号通路的变化而上调。蛋白酶体抑制剂可完全防止氯化钴介导的肌生成素蛋白减少。这些结果表明，氯化钴可能在转录后和翻译后水平上调节肌原蛋白的表达，导致成肌细胞不能分化为肌管。