VP.89 Skeletal muscle after a single bout of eccentric exercise in myotonic dystrophy type 1: a complete proteomic analysis

Abstract

Myotonic dystrophy type 1 (DM1) is a multisystemic progressive genetic disease that causes muscle weakness and wasting. Strength training has been shown to be safe and can induce maximal strength gains. However, the underlying molecular mechanisms of these maximal strength gains remain unclear. The aim of this study is to determine how a single bout of eccentric exercise modulates protein expression in DM1 individuals compared to controls. Eight men with DM1 and five healthy controls completed the study. On day zero, a biopsy of the vastus lateralis was taken. On day eight, participants completed a standardized eccentric knee extension exercise protocol of the biopsied leg on an isokinetic device. 24 hours later, on day nine, a second biopsy was taken in the same muscle. Proteomics were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS): all samples were pooled to create an ion library which was used to assess muscle protein expression in individual samples. A total of 894 proteins were identified. Protein expression and its modulation by exercise were heterogenous in DM1 individuals. The expression of 111 proteins was significantly modulated by exercise for the control subjects while 50 were significantly modulated in DM1 subjects. Of these proteins, 9 had increased their expression in both groups. This includes 4 structural proteins (FLNC, NEXN, XIRP1 and NRAP), 2 translation factors (EF2 and IF5), a ubiquitin and skeletal muscle differentiation modulator (KLHL40), a chaperone protein (HS90B) and a neutrophil serine protease inhibitor (ILEU). In both groups, a mitochondrial protein (NDUB8) had decreased its expression. Further analyses are being conducted to assess how DM1 individuals responded differently to exercise compared to healthy controls. In conclusion, despite the genetic default, DM1 muscle has some similar responses to exercise compared to healthy controls although it remains heterogenous among DM1 individuals.