鸡肌肉抗体芯片揭示了 LDHA 通过能量代谢对成肌细胞分化的调控作用。
Chicken muscle antibody array reveals the regulations of LDHA on myoblast differentiation through energy metabolism.
机构信息
Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University, Guangzhou 510642, China; State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou 510642, China; College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China.
Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University, Guangzhou 510642, China; State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou 510642, China; Lingnan Guangdong Laboratory of Agriculture, South China Agricultural University, Guangzhou 510642, China; Department of Orthaepedics and Traumatology, The Chinese University of Hong Kong, Hong Kong 999077, China.
出版信息
Int J Biol Macromol. 2024 Jan;254(Pt 1):127629. doi: 10.1016/j.ijbiomac.2023.127629. Epub 2023 Oct 25.
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.
成肌细胞的增殖和分化是骨骼肌发育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，因此在蛋白质水平上探索关键的调节因子和机制为理解骨骼肌发育提供了很大的机会。在这项研究中，我们使用鸡肌肉抗体芯片筛选出了成肌细胞增殖和分化之间的 607 种差异表达蛋白。生物功能分析揭示了能量产生过程和化合物代谢过程在肌发生中的重要性。我们的抗体芯片特别鉴定出在分化过程中 LDHA 的上调与能量代谢有关。随后的研究表明，LDHA 通过促进糖酵解和 TCA 循环，从而增强成肌细胞的分化。从机制上讲，LDHA 通过增强 NADH 循环来促进糖酵解和 TCA 循环，但抑制 ETC 氧化磷酸化，提供改善成肌细胞分化的中间代谢产物。此外，LDHA 增加的糖酵解 ATP 通过激活 Akt 磷酸化并激活 PI3K-Akt 通路，这也可能有助于促进成肌细胞分化。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种强大的工具，还确定了 LDHA 通过调节细胞 NAD 水平及其对线粒体功能的后续下游影响来调节成肌细胞分化的新作用。
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