Abstract
Background: Decreased neuromuscular activity, in terms of different models including hindlimb suspension, can result in muscular atrophy by changing different genes expression. Hdac4&5 and their downstream pathways are the two important factors involved in the preservation of muscle mass. Methods: In the current study, in order to survey the changes of Hdac4&5 and their downstream cascade mRNA expression, Wistar rats were assigned into two groups 1) weight bearing (WB) and 2) Hindlimb-suspension (HS) (n=5 in each group). Hindlimb’s rats were suspended for 14 days. After two weeks, the rats were sacrificed and the soleus and plantaris muscles were collected. Thereafter, gene expression was measured using Real time technique. Results: The results showed that 14 days hindlimb suspension decreased muscle mass in both the plantaris and soleus muscles and the latter changes definitely outweighed the former. In addition, it has been shown that the cross-sectional area of the muscle fibers of the plantaris and soleus muscles decreased and, with changes in muscle mass, the observed decrease in soleus was higher. Also, the increase in mRNA expression of Hdac4&5, Myogenin, and Gadd45a, was observed in both muscles. But the expression of the Dach2 gene was significantly reduced in the plantaris and soleus muscles of the HS group as compared to the WB group. Discussion: Hdac/Myogenin and Hdac/Dach2/Gadd45a are the two involved pathways in muscular atrophy process as a result of unloading and this could be considered as treatment candidates to resist muscular atrophy in some specific conditions such as bed rest and space flight.
Highlights
Decreased neuromuscular activity, in terms of different models including hindlimb suspension (HS), can result in muscular atrophy by changing different genes expression
In the current study, in order to survey the changes of Hdac4&5 and their downstream cascade mRNA expression, Wistar rats were assigned into 2 groups (1) weight bearing (WB) and (2) HS (n=5 in each group)
Decreased neuromuscular activity in the form of immobilization, hindlimb suspension (HS), space flight, and denervation is strongly linked to the modification of some genes such as muscle ring finger 1 (Murf-1) and atrogen-1 in skeletal muscle, which are considered as the main factors for proteolysis of muscle proteins and atrophy.[7,8,9,10]
Summary
In terms of different models including hindlimb suspension (HS), can result in muscular atrophy by changing different genes expression. Decreased neuromuscular activity in the form of immobilization, hindlimb suspension (HS), space flight, and denervation is strongly linked to the modification of some genes such as muscle ring finger 1 (Murf-1) and atrogen-1 in skeletal muscle, which are considered as the main factors for proteolysis of muscle proteins and atrophy.[7,8,9,10] It is suggested that some pathways such as histone deacetylase/ dachshund family transcription factor2/ myogenin (Hdac/Dach2/myogenin) are involved in muscular atrophy by decreased neuromuscular activity and this happens whenever neurogenic atrophy is induced by Murf-1 and atrogin-1.3,11,12 Generally, histone deacetylases, through deacetylation, can suppress or activate transcriptional process and this mediates the proliferation and growth of skeletal muscle. Some studies have shown that among the histone deacetylases family, Hdac4&5 play a major role in the maintenance and degradation of muscular proteins.[3,13] In this regard, it has been shown that increase of Hdac4&5 suppresses Dach[2] expression, which is an inhibitor of myogenin[11]; the myogenin rising regulates Murf-1 and atrogin-1 expression.[3]
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