Halevy O, Lerman O
Department of Animal Science, Faculty of Agriculture, Hebrew University, Rehovot, Israel.
J Cell Physiol. 1993 Mar;154(3):566-72. doi: 10.1002/jcp.1041540315.
Retinoic acid (RA) is known to induce differentiation in many cell systems. This induction is mediated by nuclear RA receptors (RARs), which act as transactivating factors belonging to the superfamily of steroid/thyroid nuclear receptors. In this study, effects of RA were studied in a mouse myogenic C2 cell line and in primary chicken satellite cells, the myogenic precursor cells in adult muscle. Addition of RA decreased the rate of DNA synthesis in a dose-dependent manner in both cultures. Differentiation was more rapid in cells treated with RA, and these cells exhibited large myotubes after 48 hr of incubation as compared to untreated cells, which were still proliferating. Addition of 10(-8) M RA to C2 cells elevated mRNA levels of myogenin, a skeletal muscle-specific transcription factor. In parallel, activity levels of the muscle-specific creatine kinase were enhanced in the RA-treated cells nearly twofold as compared to the untreated cells. RA treatment of both mouse C2 and chicken satellite cells caused rapid induction of the RAR-alpha mRNA levels. Maximal mRNA levels were observed after 2 to 5 hr followed by a sharp reduction to nearly zero levels at 9 hr. The RAR-alpha mRNA levels augmented in a dose-dependent manner between concentrations of 10(-10) M and 10(-8) M RA, whereas higher concentrations caused mRNA levels to decrease. These results indicate that RA induces differentiation in both adult skeletal muscle primary satellite cells and a myogenic cell line. The rapid and specific induction of RAR-alpha mRNA in these cells upon exposure to RA may suggest that this receptor is the primary target and a mediator of RA.
维甲酸（RA）已知可在许多细胞系统中诱导分化。这种诱导作用由核RA受体（RARs）介导，RARs作为属于类固醇/甲状腺核受体超家族的反式激活因子发挥作用。在本研究中，研究了RA对小鼠成肌C2细胞系和原代鸡卫星细胞（成年肌肉中的成肌前体细胞）的影响。在两种培养物中，添加RA均以剂量依赖的方式降低了DNA合成速率。用RA处理的细胞分化更快，与仍在增殖的未处理细胞相比，这些细胞在孵育48小时后表现出大的肌管。向C2细胞中添加10^(-8) M RA可提高肌细胞生成素（一种骨骼肌特异性转录因子）的mRNA水平。同时，与未处理细胞相比，RA处理的细胞中肌肉特异性肌酸激酶的活性水平提高了近两倍。对小鼠C2细胞和鸡卫星细胞进行RA处理均导致RAR-α mRNA水平迅速诱导。在2至5小时后观察到最大mRNA水平，随后在9小时急剧降至几乎零水平。在10^(-10) M至10^(-8) M RA浓度之间，RAR-α mRNA水平以剂量依赖的方式增加，而更高的浓度导致mRNA水平下降。这些结果表明，RA可诱导成年骨骼肌原代卫星细胞和成肌细胞系分化。这些细胞在暴露于RA后迅速且特异性地诱导RAR-α mRNA，这可能表明该受体是RA的主要靶点和介导因子。
