title: FoxO1 is not a key transcription factor in the regulation of myostatin (mstn-1a and mstn-1b) gene expression in trout myotubes.
abstract: In mammals, much evidence has demonstrated the important role of myostatin (MSTN) in regulating muscle mass and identified the transcription factor forkhead box O (FoxO) 1 as a key regulator of its gene expression during atrophy. However, in trout, food deprivation leads to muscle atrophy without an increase of the expression of mstn genes in the muscle. We therefore studied the relationship between FoxO1 activity and the expression of both mstn genes (mstn1a and mstn1b) in primary culture of trout myotubes. To this aim, two complementary studies were undertaken. In the former, FoxO1 protein activity was modified with insulin-like growth factor-I (IGF-I) treatment, and the consequences on the expression of both mstn genes were monitored. In the second experiment, the expression of both studied genes was modified with growth hormone (GH) treatment, and the activation of FoxO1 protein was investigated. We found that IGF-I induced the phosphorylation of FoxO1 and FoxO4. Moreover, under IGF-I stimulation, FoxO1 was no longer localized in the nucleus, indicating that this growth factor inhibited FoxO1 activity. However, IGF-I treatment had no effect on mstn1a and mstn1b expression, suggesting that FoxO1 would not regulate the expression of mstn genes in trout myotubes. Furthermore, the treatment of myotubes with GH decreased the expression of both mstn genes but has no effect on the phosphorylation of FoxO1, FoxO3, and FoxO4 nor on the nuclear translocation of FoxO1. Altogether, our results showed that mstn1a and mstn1b expressions were not associated with FoxO activity, indicating that FoxO1 is likely not a key regulator of mstn genes in trout myotubes.
authors.affiliation: Institut National de la Recherche Agronomique, UMR 1067 Nutrition Aquaculture et Génomique, Pôle d’hydrobiologie, St-Pée-sur-Nivelle, France.
authors.forename: Iban
authors.initials: I
authors.lastname: Seiliez
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sabin
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Gabillard
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D013006:Growth Hormone / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D023421:Models, Animal; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D055435:Myostatin / Q000235:genetics* / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D014337:Trout / Q000502:physiology*
chemical_list: D051858:Forkhead Transcription Factors; D055435:Myostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone