Chicken muscle antibody array reveals the regulations of LDHA on myoblast differentiation through energy metabolism
Chicken muscle antibody array reveals the regulations of LDHA on myoblast differentiation through energy metabolism
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DOI：
10.1016/j.ijbiomac.2023.127629
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发表时间：
2023-11-01
影响因子：
8.2
通讯作者：
Zhang，Xiquan
中科院分区：
文献类型：
--
作者：
Zhang，Zihao;Luo，Wen;Zhang，Xiquan
成肌细胞的增殖和分化是骨骼肌发育过程中高度动态和受调控的过程。鉴于蛋白质是大多数生物过程的执行者，在蛋白质水平上探索关键的调控因素和机制为理解骨骼肌的发育提供了大量的机会。本研究利用我们的鸡肌抗体阵列筛选出607个成肌细胞增殖分化差异表达蛋白。生物功能分析揭示了能量产生过程和复合代谢过程在肌肉发生中的重要性。我们的抗体阵列特异性地识别了分化过程中LDHA的上调，这与能量代谢有关。随后的研究表明，LDHA促进糖酵解和TCA循环，从而促进成肌细胞的分化。在机制上，LDHA通过促进NADH循环，提供促进成肌细胞分化的中间代谢产物，促进糖酵解和TCA循环，但抑制ETC的氧化磷酸化。此外，LDHA增加糖酵解ATP诱导Akt磷酸化并激活PI3K-Akt通路，这可能也有助于促进成肌细胞的分化。我们的研究不仅为探索鸡肌肉中的成肌调节因子提供了一个强有力的工具，而且还发现了LDHA通过调节细胞内NAD+水平以及随后对线粒体功能的下游影响来调节成肌细胞分化的新角色。
Myoblast proliferation and differentiation are highly dynamic and regulated processes in skeletal muscle development. Given that proteins serve as the executors for the majority of biological processes, exploring key regulatory factors and mechanisms at the protein level offers substantial opportunities for understanding the skeletal muscle development. In this study, a total of 607 differentially expressed proteins between proliferation and differentiation in myoblasts were screened out using our chicken muscle antibody array. Biological function analysis revealed the importance of energy production processes and compound metabolic processes in myogenesis. Our antibody array specifically identified an upregulation of LDHA during differentiation, which was associated with the energy metabolism. Subsequent investigation demonstrated that LDHA promoted the glycolysis and TCA cycle, thereby enhancing myoblasts differentiation. Mechanistically, LDHA promotes the glycolysis and TCA cycle but inhibits the ETC oxidative phosphorylation through enhancing the NADH cycle, providing the intermediate metabolites that improve the myoblasts differentiation. Additionally, increased glycolytic ATP by LDHA induces Akt phosphorylation and activate the PI3K-Akt pathway, which might also contribute to the promotion of myoblasts differentiation. Our studies not only present a powerful tool for exploring myogenic regulatory factors in chicken muscle, but also identify a novel role for LDHA in modulating myoblast differentiation through its regulation of cellular NAD+levels and subsequent downstream effects on mitochondrial function.