2020

Kusić, Denis; Connolly, Joanne; Kainulainen, Heikki; Semenova, Ekaterina A.; Borisov, Oleg V.; Larin, Andrey K.; Popov, Daniil V.; Generozov, Edward V.; Ahmetov, Ildus I.; Britton, Steve L.; Koch, Lauren G.; Burniston, Jatin G.

Bi-directional selection for either high- or low-responsiveness to endurance running has created divergent rat phenotypes of high-response trainers (HRT) and low-response trainers (LRT). We conducted proteome profiling of HRT and LRT gastrocnemius of 10 female rats (body weight 279 ± 35 g; n=5 LRT and n=5 HRT) from generation 8 of selection. Differential analysis of soluble proteins from gastrocnemius was conducted using label-free quantitation.Genetic association studies were conducted in 384 Russian international-level athletes (age 23.8 ± 3.4 y; 202 males and 182 females) stratified to endurance or power disciplines. Proteomic analysis encompassed 1,024 proteins, 76 of which exhibited statistically significant (P<0.05, FDR <1 %) differences between HRT and LRT muscle. There was significant enrichment of enzymes involved in glycolysis/ gluconeogenesis in LRT muscle but no enrichment of gene ontology phrases in HRT muscle. Striated muscle-specific serine/threonine-protein kinase beta (SPEGβ) exhibited the greatest difference in abundance and was 2.64-fold greater (P=0.0014) in HRT muscle. Co-immunoprecipitation identified 24 potential binding partners of SPEGβ in HRT muscle. The frequency of the G variant of the rs7564856 polymorphism that increases SPEG gene expression, was significantly greater (32.9 vs 23.8%; OR = 1.6, P = 0.009) in international-level endurance athletes (n=258) compared to power athletes (n=126) and was significantly associated (β = 8.345, P = 0.0048) with a greater proportion of slow-twitch fibres in vastus lateralis of female endurance athletes. Co-immunoprecipitation of SPEGβ in HRT muscle discovered putative interacting proteins that link with previously reported differences in transforming growth factor-β signalling in exercised muscle.