Arsenic inhibits myogenic differentiation and muscle regeneration.

Background: The incidence of low birth weights is increased in offspring of women who are exposed to high concentrations of arsenic in drinking water compared with other women. We hypothesized that effects of arsenic on birth weight may be related to effects on myogenic differentiation. Objective: W...

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Publicado en:Environmental Health Perspectives Vol. 118; no. 7; pp. 949 - 957
Autores principales: Yen Y, Tsai K, Chen Y, Huang C, Yang R, Liu S
Formato: pictorial research tables/charts Journal Article
Publicado: National Institute of Environmental Health Sciences Jul2010
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jul2010
      vid: 118
      iid: 7
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      pub: National Institute of Environmental Health Sciences
      place: Research Triangle Park, North Carolina
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        atl: Arsenic inhibits myogenic differentiation and muscle regeneration.
      aug:
        au:
          Yen Y
          Tsai K
          Chen Y
          Huang C
          Yang R
          Liu S
        affil: Institute of Toxicology College of Medicine, National Taiwan University, Taipei, Taiwan
      sug:
        subj:
          Arsenic Adverse Effects
          Cell Physiology
          Regeneration
          Analysis of Variance
          Biopsy
          Culture Media
          Descriptive Statistics
          Female
          Funding Source
          Human
          In Vitro Studies
          In Vivo Studies
          Mice
          Middle Age
          Muscle Fibers Analysis
          Staining and Labeling
          T-Tests
          Taiwan
          Middle Aged: 45-64 years
          Female
      ab: Background: The incidence of low birth weights is increased in offspring of women who are exposed to high concentrations of arsenic in drinking water compared with other women. We hypothesized that effects of arsenic on birth weight may be related to effects on myogenic differentiation. Objective: We investigated the effects of arsenic trioxide (As(2)O(3)) on the myogenic differentiation of myoblasts in vitro and muscle regeneration in vivo. Methods: C2C12 myoblasts and primary mouse and human myoblasts were cultured in differentiation media with or without As(2)O(3) (0.1-0.5 µM) for 4 days. Myogenic differentiation was assessed by myogenin and myosin heavy chain expression and multinucleated myotube formation in vitro; skeletal muscle regeneration was tested using an in vivo mouse model with experimental glycerol myopathy. Results: A submicromolar concentration of As(2)O(3) dose-dependently inhibited myogenic differentiation without apparent effects on cell viability. As(2)O(3) significantly and dose-dependently decreased phosphorylation of Akt and p70s6k proteins during myogenic differentiation. As(2)O(3)-induced inhibition in myotube formation and muscle-specific protein expression was reversed by transfection with the constitutively active form of Akt. Sections of soleus muscles stained with hematoxylin and eosin showed typical changes of injury and regeneration after local glycerol injection in mice. Regeneration of glycerol-injured soleus muscles, myogenin expression, and Akt phosphorylation were suppressed in muscles isolated from As(2)O(3)-treated mice compared with untreated mice. Conclusion: Our results suggest that As2O3 inhibits myogenic differentiation by inhibiting Aktregulated signaling.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
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        Journal Article
      ougenre: Article
    language: English
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