Striated muscle-specific serine/threonine-protein kinase beta segregates with high versus low responsiveness to endurance exercise training

Abstract

Bidirectional 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 by label-free quantitation. Genetic association studies were conducted in 384 Russian international-level athletes (age 23.8 ± 3.4 yr; 202 men and 182 women) stratified to endurance or power disciplines. Proteomic analysis encompassed 1,024 proteins, 76 of which exhibited statistically significant ( P < 0.05, false discovery rate <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 (SPEG-β) exhibited the greatest difference in abundance and was 2.64-fold greater ( P = 0.0014) in HRT muscle. Coimmunoprecipitation identified 24 potential binding partners of SPEG-β 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 with power athletes ( n = 126) and was significantly associated (β = 8.345, P = 0.0048) with a greater proportion of slow-twitch fibers in vastus lateralis of female endurance athletes. Coimmunoprecipitation of SPEG-β in HRT muscle discovered putative interacting proteins that link with previously reported differences in transforming growth factor-β signaling in exercised muscle.