title: Myostatin inactivation induces a similar muscle molecular signature in double-muscled cattle as in mice.
abstract: Myostatin (MSTN), a member of the TGF-β superfamily, is a negative regulator of skeletal muscle mass. We have previously shown that the cell survival/apoptosis pathway is a downstream target of MSTN loss-of-function in mice through the regulation of the expression or abundance of many survival and apoptotic factors. In this study, we used western-blot and quantitative PCR (qPCR) analyses to validate these novel downstream targets of MSTN in double-muscled (DM) cattle v. their controls including 260-day-old foetuses and adult cows from the INRA95 strain. MSTN loss-of-function in DM foetuses and DM cows resulted in a glycolytic shift of the muscles (e.g. upregulation of H-MyBP, PGM1 and SNTA1 and downregulation of H-FABP), activation of cell survival pathway through regulation of some components of the PI3K/Akt pathway (e.g. upregulation of DJ-1 and Gsk-3βser9/Gsk-3βtotal ratio and downregulation of PTEN) and upregulation of cell survival factors translationally controlled tumour protein (14-3-3E, Pink1). We also found a lower abundance of pro-apoptotic transcripts and/or proteins (Caspase-3, caspase-8, caspase-9, BID, ID2 and Daxx) and a higher expression of anti-apoptotic transcripts (Traf2 and Bcl2l2) in DM muscles. All together, these results are in favour of activation of the cell survival pathway and loss of apoptosis pathway within the muscles of DM animals. Alteration of both pathways may increase myonuclear or satellite cell survival, which is crucial for protein synthesis. This could contribute to muscle hypertrophy in DM foetuses and DM cows.
authors.affiliation: INRA, UR1213, Unité de Recherches sur les Herbivores, Equipe Croissance et Métabolisme du Muscle, Centre Clermont-Ferrand/Theix, 63122 Saint-Genès-Champanelle, France.
authors.forename: I
authors.initials: I
authors.lastname: Chelh
authors.forename: B
authors.initials: B
authors.lastname: Picard
authors.forename: J-F
authors.initials: JF
authors.lastname: Hocquette
authors.forename: I
authors.initials: I
authors.lastname: Cassar-Malek