Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 04310, Republic of Korea.
Department of Molecular Cell Biology, Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea.
Toxicol Lett. 2018 Aug;292:12-19. doi: 10.1016/j.toxlet.2018.04.019. Epub 2018 Apr 20.
Bisphenol A (BPA), one of the most widespread endocrine disrupting chemicals, is known as an artificial estrogen, which interacts with estrogen receptor (ER). In this study, we investigated the effects of BPA and estradiol on myoblast differentiation and the underlying signaling mechanism. Exposure to BPA (0.01-1 μM) in mouse myoblast C2C12 cells attenuated myogenic differentiation via the reduced expression of muscle-specific genes, such as myosin heavy chain (MHC), MyoD, and Myogenin, without the alteration of cell proliferation and viability. BPA-exposed C2C12 myoblasts also showed a reduction of Akt phosphorylation ((37-61) %, p < 0.001), a key event for myogenesis. Similarly to BPA, estradiol (0.01-1 μM) reduced the expression of muscle-specific proteins and the formation of multinucleated myotubes, and attenuated the muscle differentiation-specific phosphorylation of Akt ((42-59) %, p < 0.001). We conclude that BPA and estradiol suppress myogenic differentiation through the inhibition of Akt signaling.
双酚 A（BPA）是一种广泛存在的内分泌干扰化学物质，被称为人工雌激素，可与雌激素受体（ER）相互作用。在这项研究中，我们研究了 BPA 和雌二醇对成肌细胞分化的影响及其潜在的信号机制。在小鼠成肌细胞 C2C12 中，BPA（0.01-1 μM）的暴露通过降低肌球蛋白重链（MHC）、MyoD 和 Myogenin 等肌肉特异性基因的表达来减弱成肌分化，而不改变细胞增殖和活力。BPA 暴露的 C2C12 成肌细胞的 Akt 磷酸化（(37-61) %，p < 0.001）也减少，这是成肌作用的关键事件。与 BPA 相似，雌二醇（0.01-1 μM）也降低了肌肉特异性蛋白的表达和多核肌管的形成，并减弱了 Akt 的肌肉分化特异性磷酸化（(42-59) %，p < 0.001）。我们得出结论，BPA 和雌二醇通过抑制 Akt 信号通路来抑制成肌分化。
