title: Reduced expression of MyHC slow isoform in rat soleus during unloading is accompanied by alterations of endogenous inhibitors of calcineurin/NFAT signaling pathway.
abstract: Under muscle disuse conditions decrease of expression of MyHC of slow type, and sometimes of type IIa, as well as upregulation of expression of IIb and IId/x isoforms were observed. Through dephosphorylation and entry of NFAT molecules to the nucleus calcineurin/NFATc1 signaling pathway promotes upregulation of the slow MyHC expression. We supposed that downregulation of calcineurin pathway took place during unloading. The study was aimed to analyze the states of the myonuclear NFAT inhibitors calsarcin I (CSI) and calsarcin II (CSII) (also referred to as myozenin II and I) and GSK3β in rat soleus during hindlimb suspension (HS). Male Wistar rats were subjected to 3, 7 and 14 day of HS. We found that after 3 days of HS the content of CSII mRNA twofold increased in soleus as compared to the controls. This level was increased by more than fivefold (as compared to control) after 2 weeks of HS. The increase of CSII mRNA expression may be explained as the mechanism of stabilization of fast phenotype. We found that from the 3 day till 14 day of HS the content of MuRF-1 and MuRF-2 in the nuclear fraction fourfold to fivefold increased in HS soleus. We supposed that nuclear import of the MuRFs allows to promote CSII expression during unloading. We also observed the decline of the phosphorylated GSK3β content in the nuclear extract of the soleus tissue. Thus decline of slow MyHC expression characteristic for the unloading conditions is accompanied with the increased expression and activation of the factors known to prevent NFAT accumulation in the myonuclei.
authors.affiliation: Institute of Biomedical Problems, Russian Academy of Sciences, 76a, Khoroshevskoye Shosse, Moscow, Russia, 123007.
authors.forename: Yulia N
authors.initials: YN
authors.lastname: Lomonosova
authors.affiliation: Institute of Biomedical Problems, Russian Academy of Sciences, 76a, Khoroshevskoye Shosse, Moscow, Russia, 123007.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Turtikova
authors.affiliation: Institute of Biomedical Problems, Russian Academy of Sciences, 76a, Khoroshevskoye Shosse, Moscow, Russia, 123007. bshenkman@mail.ru.
authors.forename: Boris S
authors.initials: BS
authors.lastname: Shenkman
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006614:Hindlimb; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D008840:Microfilament Proteins; D009124:Muscle Proteins; C524829:Myoz2 protein, rat; D050778:NFATC Transcription Factors; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D019703:Calcineurin; D018995:Myosin Heavy Chains
keywords: Calsarcin-1,-2; Hindlimb suspension; MuRF-1,-2; Myosin heavy chains expression