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Rapid decline in MyHC I(β) mRNA expression in rat soleus during hindlimb unloading is associated with AMPK dephosphorylation
Author(s) -
Vilchinskaya Natalia A.,
Mochalova Ekaterina P.,
Nemirovskaya Tatiana L.,
Mirzoev Timur M.,
Turtikova Olga V.,
Shenkman Boris S.
Publication year - 2017
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp275184
Subject(s) - ampk , dephosphorylation , myosin , protein kinase a , phosphorylation , histone deacetylase , gene isoform , chemistry , soleus muscle , myosin light chain kinase , skeletal muscle , microbiology and biotechnology , biology , endocrinology , histone , biochemistry , gene , phosphatase
Key points Inactivation of a skeletal muscle results in slow to fast myosin heavy chain (MyHC) shift. AMP‐activated protein kinase (AMPK) can be implicated in the regulation of genes encoding the slow MyHC isoform. Here we report that AMPK dephosphorylation after 24 h of mechanical unloading can contribute to histone deacetylase (HDAC) nuclear translocation; activation of AMPK prevents HDAC4 nuclear accumulation after 24 h of unloading and AMPK dephosphorylation inhibits slow MyHC expression following 24 h of unloading. Our data indicate that AMPK dephosphorylation during the first 24 h of mechanical unloading has a significant impact on the expression of MyHC isoforms in rat soleus causing a decrease in MyHC I(β) pre‐mRNA and mRNA expression as well as MyHC IIa mRNA expression.Abstract One of the key events that occurs during skeletal muscle inactivation is a change in myosin phenotype, i.e. increased expression of fast isoforms and decreased expression of the slow isoform of myosin heavy chain (MyHC). It is known that calcineurin/nuclear factor of activated T‐cells and AMP‐activated protein kinase (AMPK) can regulate the expression of genes encoding MyHC slow isoform. Earlier, we found a significant decrease in phosphorylated AMPK in rat soleus after 24 h of hindlimb unloading (HU). We hypothesized that a decrease in AMPK phosphorylation and subsequent histone deacetylase (HDAC) nuclear translocation can be one of the triggering events leading to a reduced expression of slow MyHC. To test this hypothesis, Wistar rats were treated with AMPK activator (AICAR) for 6 days before HU as well as during 24 h of HU. We discovered that AICAR treatment prevented a decrease in pre‐mRNA and mRNA expression of MyHC I as well as MyHC IIa mRNA expression. Twenty‐four hours of hindlimb suspension resulted in HDAC4 accumulation in the nuclei of rat soleus but AICAR pretreatment prevented this accumulation. The results of the study indicate that AMPK dephosphorylation after 24 h of HU had a significant impact on the MyHC I and MyHC IIa mRNA expression in rat soleus. AMPK dephosphorylation also contributed to HDAC4 translocation to the nuclei of soleus muscle fibres, suggesting an important role of HDAC4 as an epigenetic regulator in the process of myosin phenotype transformation.