HDAC4 Is Indispensable for Reduced Slow Myosin Expression at the Early Stage of Hindlimb Unloading in Rat Soleus Muscle

It is well known that reduced contractile activity of the main postural soleus muscle during long-term bedrest, immobilization, hindlimb unloading, and space flight leads to increased expression of fast isoforms and decreased expression of the slow isoform of myosin heavy chain (MyHC). The signaling...

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Autores principales:	Inna I. Paramonova, Natalia A. Vilchinskaya, Boris S. Shenkman
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hindlimb unloading Tasqiunimod MyHC HDAC4 soleus muscle Medicine R Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/b858ef8b4b1f4fc0af047323449ffc27
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spelling	oai:doaj.org-article:b858ef8b4b1f4fc0af047323449ffc272021-11-25T18:39:52ZHDAC4 Is Indispensable for Reduced Slow Myosin Expression at the Early Stage of Hindlimb Unloading in Rat Soleus Muscle10.3390/ph141111671424-8247https://doaj.org/article/b858ef8b4b1f4fc0af047323449ffc272021-11-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1167https://doaj.org/toc/1424-8247It is well known that reduced contractile activity of the main postural soleus muscle during long-term bedrest, immobilization, hindlimb unloading, and space flight leads to increased expression of fast isoforms and decreased expression of the slow isoform of myosin heavy chain (MyHC). The signaling cascade such as HDAC4/MEF2-D pathway is well-known to take part in regulating MyHC I gene expression. Earlier, we found a significant increase of HDAC4 in myonuclei due to AMPK dephosphorylation during 24 h of hindlimb unloading via hindlimb suspension (HU) and it had 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. We hypothesized that dephosphorylated HDAC4 translocates into the nuclei and can lead to a reduced expression of slow MyHC. To test this hypothesis, Wistar rats were treated with HDAC4 inhibitor (Tasquinimod) for 7 days before HU as well as during 24 h of HU. We discovered that Tasquinimod treatment prevented a decrease in pre-mRNA expression of MyHC I. Furthermore, 24 h of hindlimb suspension resulted in HDAC4 nuclear accumulation of rat soleus but Tasquinimod pretreatment prevented this accumulation. The results of the study indicate that HDAC4 after 24 h of HU had a significant impact on the precursor MyHC I mRNA expression in rat soleus.Inna I. ParamonovaNatalia A. VilchinskayaBoris S. ShenkmanMDPI AGarticlehindlimb unloadingTasqiunimodMyHCHDAC4soleus muscleMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1167, p 1167 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hindlimb unloading Tasqiunimod MyHC HDAC4 soleus muscle Medicine R Pharmacy and materia medica RS1-441
spellingShingle	hindlimb unloading Tasqiunimod MyHC HDAC4 soleus muscle Medicine R Pharmacy and materia medica RS1-441 Inna I. Paramonova Natalia A. Vilchinskaya Boris S. Shenkman HDAC4 Is Indispensable for Reduced Slow Myosin Expression at the Early Stage of Hindlimb Unloading in Rat Soleus Muscle
description	It is well known that reduced contractile activity of the main postural soleus muscle during long-term bedrest, immobilization, hindlimb unloading, and space flight leads to increased expression of fast isoforms and decreased expression of the slow isoform of myosin heavy chain (MyHC). The signaling cascade such as HDAC4/MEF2-D pathway is well-known to take part in regulating MyHC I gene expression. Earlier, we found a significant increase of HDAC4 in myonuclei due to AMPK dephosphorylation during 24 h of hindlimb unloading via hindlimb suspension (HU) and it had 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. We hypothesized that dephosphorylated HDAC4 translocates into the nuclei and can lead to a reduced expression of slow MyHC. To test this hypothesis, Wistar rats were treated with HDAC4 inhibitor (Tasquinimod) for 7 days before HU as well as during 24 h of HU. We discovered that Tasquinimod treatment prevented a decrease in pre-mRNA expression of MyHC I. Furthermore, 24 h of hindlimb suspension resulted in HDAC4 nuclear accumulation of rat soleus but Tasquinimod pretreatment prevented this accumulation. The results of the study indicate that HDAC4 after 24 h of HU had a significant impact on the precursor MyHC I mRNA expression in rat soleus.
format	article
author	Inna I. Paramonova Natalia A. Vilchinskaya Boris S. Shenkman
author_facet	Inna I. Paramonova Natalia A. Vilchinskaya Boris S. Shenkman
author_sort	Inna I. Paramonova
title	HDAC4 Is Indispensable for Reduced Slow Myosin Expression at the Early Stage of Hindlimb Unloading in Rat Soleus Muscle
title_short	HDAC4 Is Indispensable for Reduced Slow Myosin Expression at the Early Stage of Hindlimb Unloading in Rat Soleus Muscle
title_full	HDAC4 Is Indispensable for Reduced Slow Myosin Expression at the Early Stage of Hindlimb Unloading in Rat Soleus Muscle
title_fullStr	HDAC4 Is Indispensable for Reduced Slow Myosin Expression at the Early Stage of Hindlimb Unloading in Rat Soleus Muscle
title_full_unstemmed	HDAC4 Is Indispensable for Reduced Slow Myosin Expression at the Early Stage of Hindlimb Unloading in Rat Soleus Muscle
title_sort	hdac4 is indispensable for reduced slow myosin expression at the early stage of hindlimb unloading in rat soleus muscle
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b858ef8b4b1f4fc0af047323449ffc27
work_keys_str_mv	AT innaiparamonova hdac4isindispensableforreducedslowmyosinexpressionattheearlystageofhindlimbunloadinginratsoleusmuscle AT nataliaavilchinskaya hdac4isindispensableforreducedslowmyosinexpressionattheearlystageofhindlimbunloadinginratsoleusmuscle AT borissshenkman hdac4isindispensableforreducedslowmyosinexpressionattheearlystageofhindlimbunloadinginratsoleusmuscle
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HDAC4 Is Indispensable for Reduced Slow Myosin Expression at the Early Stage of Hindlimb Unloading in Rat Soleus Muscle

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