Abstract The role of histone deacetylases 4/5 (HDAC4/5) in the activation of myogenin and E3 ligases (MuRF1 and MAFbx) under functional unloading of m. soleus was studied. For this purpose, trichostatin A, a histone deacetylase inhibitor, was used in suspended rats. Wistar rats (24 three-month-old males) were divided into three groups (eight in each). One group served as a control (C), the second (HS) and third groups were suspended for 3 days (the rats of group 3 were intraperitoneally administered trichostatin A at a dose of 0.6 mg/kg of body mass per day (HST)). The rats were killed with an overdose of nembutal (75 mg/kg of mass), and m. soleus was immediately frozen in liquid nitrogen. In the HST group, a significant decrease in the HDAC4 protein content in the nuclear fraction (in contrast to the HS group) and its increase in the cytoplasmic fraction (relative to the control ( p < 0.05)) were found. The administration of trichostatin A prevented changes in the HDAC4 content in the nucleus (relative to the C group), whereas the HDAC5 content was significantly reduced ( p < 0.05) in the HS group. Thus, the drug prevented the effect of functional unloading on the nuclear localization of HDAC 4/5. The level of myogenin transcription factor in the HST group of rats did not differ from that in the control, while it was significantly higher in the HS group ( p < 0.05). The expression of mRNA of E3 ligase atrogin-1/MAFbx in the HST rats was the same as in the control group and was significantly higher in the HS group ( p < 0.05). The expression of mRNA of E3 ligase MuRF1in both groups was increased compared to the controls (regardless of the drug administration). Conclusion: HDAC4/5 regulates the expression of myogenin and E3 ligase atrogin-1/MAFbx. Inhibition of HDAC4/5 does not affect the regulation of the expression of E3 ligase MuRF1.

中文翻译：

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IIa 类 HDAC 在肌肉卸载下 E3 连接酶 ATROGIN-1/MAFbx 和 MuRF1 表达中的作用

摘要 组蛋白去乙酰化酶 4/5 (HDAC4/5) 在肌细胞生成素和 E3 连接酶 (MuRF1 和 MAFbx) 的功能卸载中的作用。比目鱼进行了研究。为此，曲古抑菌素 A，一种组蛋白脱乙酰酶抑制剂，用于悬浮大鼠。Wistar 大鼠（24 只三个月大的雄性）被分成三组（每组八只）。一组作为对照（C），第二组（HS）和第三组暂停3天（第3组大鼠以0.6mg / kg体重/天（HST）的剂量腹腔注射曲古抑素A ）。用过量的戊巴比妥（75 毫克/千克质量）杀死大鼠，并用 m. 比目鱼立即被冷冻在液氮中。在 HST 组中，发现核部分中 HDAC4 蛋白含量显着降低（与 HS 组相比）及其细胞质部分的增加（相对于对照（p < 0.05））。曲古抑菌素 A 的给药阻止了细胞核中 HDAC4 含量的变化（相对于 C 组），而 HDAC5 含量在 HS 组中显着降低（p < 0.05）。因此，该药物阻止了功能性卸载对 HDAC 4/5 核定位的影响。HST组大鼠肌细胞生成素转录因子水平与对照组无差异，而HS组显着升高（p<0.05）。HST组大鼠E3连接酶atrogin-1/MAFbx mRNA的表达与对照组相同，HS组显着升高（ p < 0.05）。与对照组相比，两组E3连接酶MuRF1的mRNA表达均增加（与给药无关）。结论：HDAC4/5 调节肌细胞生成素和 E3 连接酶 atrogin-1/MAFbx 的表达。HDAC4/5 的抑制不影响 E3 连接酶 MuRF1 表达的调节。