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

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

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.

Keywords: TTN; s: gravitational unloading; skeletal muscle; titin.

MeSH terms

  • Animals
  • Benzamides / pharmacology*
  • Calpain / metabolism
  • Connectin / genetics
  • Connectin / metabolism*
  • Disease Models, Animal
  • Gene Expression / drug effects
  • Hindlimb Suspension / methods
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism*
  • Male
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / drug therapy*
  • Muscular Atrophy / genetics
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / pathology
  • Proteolysis / drug effects
  • Rats
  • Rats, Wistar

Substances

  • Benzamides
  • Connectin
  • Histone Deacetylase Inhibitors
  • LMK-235
  • Ttn protein, rat
  • Calpain
  • Capn1 protein, rat
  • HDAC4 protein, rat
  • Hdac5 protein, rat
  • Histone Deacetylases