Striated muscle-specific serine/threonine-protein kinase beta (SPEGβ) segregates with high- versus low-responsiveness to endurance exercise training
Kusić, D., Connolly, J., Kainulainen, H., Semenova, E. A., Borisov, O. V., Larin, A. K., Popov, D. V., Generozov, E. V., Ahmetov, I. I., Britton, S. L., Koch, L. G., & Burniston, J. G. (2020). Striated muscle-specific serine/threonine-protein kinase beta (SPEGβ) segregates with high- versus low-responsiveness to endurance exercise training. Physiological Genomics, 52(1), 35-46. https://doi.org/10.1152/physiolgenomics.00103.2019
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Physiological GenomicsAuthors
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2020Copyright
© 2019, Physiological Genomics
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.
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- Liikuntatieteiden tiedekunta [2056]
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The exercise rat models are funded by the Office of Research Infrastructure Programs grant P40OD021331 from the National Institutes of Health. The rat models for low and high exercise response to training are maintained as an international resource with support from the Department of Physiology & Pharmacology, University of Toledo College of Medicine, Toledo, OH. Contact LGK Lauren.Koch2@UToledo.Edu or SLB brittons@umich.edu for information on the exercise rat models. The Russian study was supported in part by grant from the Russian Science Foundation (Grant No. 17‐15‐01436: "Comprehensive analysis of the contribution of genetic, epigenetic and environmental factors in the individual variability of the composition of human muscle fibers”; DNA sample collection, genotyping and determination of muscle fiber composition of Russian subjects).

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