2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin induces alterations in myogenic differentiation of C2C12 cells. (April 2018)

• Record Type: Journal Article
• Authors: Xie, Heidi Q.; Xia, Yingjie; Xu, Tuan; Chen, Yangsheng; Fu, Hualing; Li, Yunping; Luo, Yali; Xu, Li; Tsim, Karl W.K.; Zhao, Bin
• Is Part Of: Environmental pollution. Volume 235(2018)
• Page Start: 965
• Page End: 973
• Publication Date: 2018-04
• Subjects: 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin -- Acetylcholinesterase -- C2C12 cells -- Myogenic differentiation -- Aryl hydrocarbon receptor (AhR); Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2017.12.016
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: 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. Graphical abstract: Image 1 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. Abstract : This work is the first study that demonstrates the suppression of myogenesis and the expression of AChE during myogenic differentiation induced by dioxin.