Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Moscow, Russia.
Institute of Cell Biophysics, Russian Academy of Sciences - a Separate Division of Federal Research Center Pushchino Scientific Center for Biological Research, Russian Academy of Sciences, Pushchino, Moscow region, Russia.
Bull Exp Biol Med. 2020 Aug;169(4):450-457. doi: 10.1007/s10517-020-04907-5. Epub 2020 Sep 5.
We studied the effect of histone deacetylase 1 (HDAC1) inhibition on titin content and expression of TTN gene in rat m. soleus after 3-day gravitational unloading. Male Wistar rats weighing 210±10 g were randomly divided into 3 groups: control, 3-day hindlimb suspension, and 3-day hindlimb suspension and injection of HDAC1 inhibitor CI-994 (1 mg/kg/day). In hindlimb-suspended rats, the muscle weight/animal body weight ratio was reduced by 13.8% (p<0.05) in comparison with the control, which attested to the development of atrophic changes in the soleus muscle. This was associated with a decrease in the content of NT-isoform of intact titin-1 by 28.6% (p˂0.05) and an increase in TTN gene expression by 1.81 times (p˂0.05) in the soleus muscle. Inhibition of HDAC1 by CI-994 during 3-day hindlimb suspension prevented the decrease in titin content and development of atrophy in rat soleus muscle. No significant differences in the TTN gene expression from the control were found. These results can be used when finding the ways of preventing or reducing the negative changes in the muscle caused by gravitational unloading.
我们研究了组蛋白去乙酰化酶 1（HDAC1）抑制剂对 3 天失重后大鼠比目鱼肌肌联蛋白含量和 TTN 基因表达的影响。雄性 Wistar 大鼠体重 210±10 g，随机分为 3 组：对照组、3 天悬吊组和 3 天悬吊及注射 HDAC1 抑制剂 CI-994（1 mg/kg/天）组。与对照组相比，悬吊组大鼠的肌肉重量/动物体重比降低了 13.8%（p<0.05），这证明了比目鱼肌发生了萎缩性变化。这与完整肌联蛋白-1 的 NT-同种型含量下降 28.6%（p<0.05）和 TTN 基因表达增加 1.81 倍（p<0.05）有关。在 3 天的悬吊期间，CI-994 抑制 HDAC1 可防止肌联蛋白含量下降和大鼠比目鱼肌萎缩的发展。与对照组相比，TTN 基因表达没有显著差异。这些结果可用于寻找预防或减少重力卸载引起的肌肉负面变化的方法。
