Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, 193 Tunxi Road, Hefei, Anhui 230009, PR China; School of Food and Biological Engineering, Hefei University of Technology, No. 193 of Tunxi Road, Baohe District, 230009 Hefei, China.
Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, 193 Tunxi Road, Hefei, Anhui 230009, PR China; School of Food and Biological Engineering, Hefei University of Technology, No. 193 of Tunxi Road, Baohe District, 230009 Hefei, China.
Toxicology. 2023 Nov;499:153639. doi: 10.1016/j.tox.2023.153639. Epub 2023 Oct 4.
Myogenesis is a crucial process governing skeletal muscle development and homeostasis. Lead (Pb) exposure impaired the development and the health of bones, which slows the growth of children. However, it is far from clear what exactly the effects of Pb on skeletal muscle development are. In this study, C2C12 cells are commonly used as an in vitro model of muscle regeneration due to their ability to transition from a proliferative phase into differentiated myofibers. The dose of 1, 5, and 10 μM Pb were adopted to study the toxicity of Pb on C2C12 proliferation and differentiation. First, the effects of Pb on cell viability were detected and the results demonstrated that 5 μM and 10 μM Pb exposure decreased cell viability, while 1 μM Pb exposure has no obvious effects on cell viability. Then, 1-10 μM Pb exposure seriously reduced the C2C12 myoblasts differentiation, with the decrease of myogenic differentiation marker genes expression, including Muscle creatine kinase (MCK), Myosin Heavy Chain 4 (MYH4), Myogenin (MYOG), Myogenic Differentiation (MYOD). What's more, it was found that the epigenetic modifier histone deacetylase-2 (HDAC2) was upregulated after Pb exposure on C2C12 myoblasts. Further studies conclusively showed knockdown of HDAC2 ameliorated Pb-damaged C2C12 myoblasts differentiation, indicating HDAC2 plays a vital role in the Pb-induced C2C12 myoblasts differentiation deficits. In summary, these results demonstrated that Pb exposure inhibited C2C12 myoblasts differentiation by regulating HDAC2.
成肌作用是一个控制骨骼肌发育和稳态的关键过程。铅（Pb）暴露会损害骨骼的发育和健康，从而减缓儿童的生长速度。然而，目前尚不清楚 Pb 对骨骼肌发育的确切影响是什么。在这项研究中，由于 C2C12 细胞能够从增殖期过渡到分化的肌纤维，因此通常将其用作肌肉再生的体外模型。采用 1、5 和 10 μM Pb 剂量来研究 Pb 对 C2C12 增殖和分化的毒性。首先，检测了 Pb 对细胞活力的影响，结果表明 5 μM 和 10 μM Pb 暴露会降低细胞活力，而 1 μM Pb 暴露对细胞活力没有明显影响。然后，1-10 μM Pb 暴露严重减少了 C2C12 成肌细胞的分化，肌生成分化标记基因的表达减少，包括肌酸激酶（MCK）、肌球蛋白重链 4（MYH4）、成肌因子（MYOG）和肌生成分化（MYOD）。更重要的是，发现在 C2C12 成肌细胞中 Pb 暴露后表观遗传修饰酶组蛋白去乙酰化酶-2（HDAC2）上调。进一步的研究表明，HDAC2 的敲低改善了 Pb 损伤的 C2C12 成肌细胞分化，表明 HDAC2 在 Pb 诱导的 C2C12 成肌细胞分化缺陷中发挥重要作用。总之，这些结果表明 Pb 暴露通过调节 HDAC2 抑制 C2C12 成肌细胞分化。
