2,3,7,8-Tetrachlorodibenzo-p-dioxin induces alterations in myogenic differentiation of C2C12 cells

Highlights: • Direct cellular and molecular evidence for myogenesis disturbances of dioxin. • Dioxin suppresses myotube formation of C2C12 cells. • Dioxin dose-dependently inhibits AChE expression during myogenic differentiation. • AhR does not directly mediate the dioxin-induced AChE suppression in C2C12 cells. Dioxin-induced toxicities that affect the development of the motor system have been proposed since many years. However, cellular evidence and the molecular basis for the effects are limited. In this study, a cultured mouse myoblast cell line, C2C12, was utilized to examine the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on myogenic differentiation and expression of acetylcholinesterase (AChE), a neuromuscular transmission-related gene. The results showed that TCDD exposure at 10⁻¹⁰ M repressed the myotube formation of C2C12 cells by disturbing the fusion process and suppressing the expression of myosin heavy chain, a myobute structural protein, and not by induction of cytotoxicity. Furthermore, TCDD dose dependently suppressed the transcriptional expression and enzymatic activity of AChE during the myogenic differentiation, particularly in the middle stage. However, the administration of aryl hydrocarbon receptor antagonists, CH223191 and alpha-naphthoflavone, did not completely reverse the TCDD-induced downregulation of muscular AChE during myogenic differentiation. These findings suggest that low dose exposure to dioxin may result in disturbances of muscle differentiation and neuromuscular transmission.