Bisphenol A and estradiol impede myoblast differentiation through down-regulating Akt signaling pathway

Toxicol Lett. 2018 Aug:292:12-19. doi: 10.1016/j.toxlet.2018.04.019. Epub 2018 Apr 20.

Abstract

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.

Keywords: Akt signaling; Bisphenol A; Estradiol; Myoblast differentiation.

MeSH terms

  • Animals
  • Benzhydryl Compounds / toxicity*
  • Cell Differentiation / drug effects*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Endocrine Disruptors / toxicity*
  • Estradiol / toxicity*
  • Gene Expression Regulation
  • Mice
  • Muscle Development / drug effects*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Myoblasts / drug effects*
  • Myoblasts / enzymology
  • Myoblasts / pathology
  • Phenols / toxicity*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Muscle Proteins
  • Phenols
  • Estradiol
  • Proto-Oncogene Proteins c-akt
  • bisphenol A