Arsenic inhibits myogenic differentiation and muscle regeneration.
Arsenic inhibits myogenic differentiation and muscle regeneration.
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DOI：
10.1289/ehp.0901525
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发表时间：
2010-07
影响因子：
10.4
通讯作者：
Liu SH
中科院分区：
文献类型：
--
作者：
Yen YP;Tsai KS;Chen YW;Huang CF;Yang RS;Liu SH
与其他女性相比，接触饮用水中高浓度砷的女性的后代低出生体重的发生率会增加。我们推测砷对出生体重的影响可能与对肌源性分化的影响有关。本实验研究了三氧化二砷（As_2O_3）对体外培养成肌细胞成肌分化和体内肌肉再生的影响。将C2 C12成肌细胞以及原代小鼠和人成肌细胞在含或不含As 2 O3（0.1-0.5 μM）的分化培养基中培养4天。成肌分化进行了评估，肌细胞生成素和肌球蛋白重链的表达和多核肌管形成在体外骨骼肌再生进行了测试，在体内小鼠模型与实验甘油肌病。亚微摩尔浓度的As 2 O3剂量依赖性地抑制成肌分化，对细胞活力没有明显的影响。As_2O_3可显著降低Akt和p70 s6 k蛋白的磷酸化水平，并呈剂量依赖性。As 2 O3诱导的肌管形成和肌肉特异性蛋白表达的抑制被逆转与Akt的组成型活性形式的转染。小鼠比目鱼肌局部注射甘油后，苏木精-伊红染色切片显示出典型的损伤与再生改变。甘油损伤比目鱼肌的再生，肌细胞生成素的表达，和Akt磷酸化被抑制在肌肉中分离的As 2 O3处理的小鼠与未处理的小鼠相比。我们的研究结果表明，As 2 O3通过抑制Akt调节的信号转导抑制肌细胞分化。
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. We investigated the effects of arsenic trioxide (As2O3) on the myogenic differentiation of myoblasts in vitro and muscle regeneration in vivo. C2C12 myoblasts and primary mouse and human myoblasts were cultured in differentiation media with or without As2O3 (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. A submicromolar concentration of As2O3 dose-dependently inhibited myogenic differentiation without apparent effects on cell viability. As2O3 significantly and dose-dependently decreased phosphorylation of Akt and p70s6k proteins during myogenic differentiation. As2O3-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 As2O3-treated mice compared with untreated mice. Our results suggest that As2O3 inhibits myogenic differentiation by inhibiting Akt-regulated signaling.
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影响因子：
12.7
作者：
KAWAI, H;NISHINO, H;IWASA, M
通讯作者：
IWASA, M
影响因子：
56.9
作者：
HALEVY, O;NOVITCH, BG;LASSAR, AB
通讯作者：
LASSAR, AB
DOI：
10.1016/s1383-5742(97)00015-x
发表时间：
1997-06-01
影响因子：
5.3
作者：
Kachinskas, DJ;Qin, Q;Rice, RH
通讯作者：
Rice, RH
影响因子：
3.9
作者：
Dummler, B.;Hemmings, B. A.
通讯作者：
Hemmings, B. A.
影响因子：
4
作者：
Brameld, JM;Mostyn, A;Symonds, ME
通讯作者：
Symonds, ME