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组蛋白去乙酰化酶 4 和 5 的抑制可减少萎缩大鼠比目鱼肌肌联蛋白的蛋白水解，并防止 TTN 基因表达减少。

Inhibition of Histone Deacetylases 4 and 5 Reduces Titin Proteolysis and Prevents Reduction of TTN Gene Expression in Atrophied Rat Soleus Muscle after Seven-Day Hindlimb Unloading.

机构信息

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia.

Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Russia.

出版信息

Dokl Biochem Biophys. 2020 Nov;495(1):338-341. doi: 10.1134/S1607672920060058. Epub 2020 Dec 25.

DOI:10.1134/S1607672920060058
PMID:33368047
Abstract

The effect of HDACs 4 and 5 on the level of atrophy, calpain-1 and titin content, and TTN gene expression in rat soleus after 7-day gravitational unloading (hindlimb suspension model) was studied. The development of atrophic changes induced by gravitational unloading in rat soleus was accompanied by an increase in the calpain-1 content, an increase in titin proteolysis, and a decrease in the mRNA content of the protein. Inhibition of HDACs 4 and 5 did not eliminate the development of unloading-induced atrophy but significantly prevented proteolysis of titin and the decrease in the TTN gene expression.

摘要

研究了组蛋白去乙酰化酶 4 和 5 对 7 天失重（后肢悬吊模型）后大鼠比目鱼肌萎缩程度、钙蛋白酶-1 和肌联蛋白含量以及 TTN 基因表达的影响。重力卸载引起的大鼠比目鱼肌萎缩变化的发展伴随着钙蛋白酶-1 含量的增加、肌联蛋白的降解增加以及蛋白质的 mRNA 含量的减少。抑制组蛋白去乙酰化酶 4 和 5 并没有消除去负荷诱导的萎缩的发展，但显著阻止了肌联蛋白的降解和 TTN 基因表达的减少。

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本文引用的文献

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Nebulin and titin modulate cross-bridge cycling and length-dependent calcium sensitivity.肌联蛋白和titin 调节横桥循环和长度依赖性钙敏感性。
J Gen Physiol. 2019 May 6;151(5):680-704. doi: 10.1085/jgp.201812165. Epub 2019 Apr 4.
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Regulation of Protein Synthesis in Inactivated Skeletal Muscle: Signal Inputs, Protein Kinase Cascades, and Ribosome Biogenesis.失活骨骼肌中蛋白质合成的调控：信号输入、蛋白激酶级联反应和核糖体生物发生
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IKKβ抑制对E3泛素连接酶表达及卸载诱导的骨骼肌萎缩的矛盾效应。
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Calpain-dependent regulation of the skeletal muscle atrophy following unloading.钙蛋白酶依赖性调节卸载后骨骼肌萎缩
Arch Biochem Biophys. 2015 Oct 15;584:36-41. doi: 10.1016/j.abb.2015.07.011. Epub 2015 Aug 18.
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Histone deacetylase (HDAC) inhibitors with a novel connecting unit linker region reveal a selectivity profile for HDAC4 and HDAC5 with improved activity against chemoresistant cancer cells.新型连接单元连接区的组蛋白去乙酰化酶 (HDAC) 抑制剂揭示了对 HDAC4 和 HDAC5 的选择性特征，并且对耐药性癌细胞的活性得到改善。
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Calpain/calpastatin activities and substrate depletion patterns during hindlimb unweighting and reweighting in skeletal muscle.后肢去负荷和再负荷过程中骨骼肌中钙蛋白酶/钙蛋白酶抑制蛋白的活性及底物消耗模式
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