ACTN3 genotype influences skeletal muscle mass regulation and response to dexamethasone.

Autor:	Seto JT; Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, VIC, Australia.; Department of Paediatrics, University of Melbourne, The Royal Children's Hospital, Melbourne, VIC, Australia., Roeszler KN; Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, VIC, Australia.; Department of Paediatrics, University of Melbourne, The Royal Children's Hospital, Melbourne, VIC, Australia., Meehan LR; Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, VIC, Australia., Wood HD; Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, VIC, Australia., Tiong C; Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, VIC, Australia., Bek L; Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, VIC, Australia.; Department of Paediatrics, University of Melbourne, The Royal Children's Hospital, Melbourne, VIC, Australia., Lee SF; Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, VIC, Australia., Shah M; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia., Quinlan KGR; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia., Gregorevic P; Centre for Muscle Research, Department of Physiology, University of Melbourne, Melbourne, VIC, Australia.; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.; Department of Neurology, University of Washington, Seattle, WA, USA., Houweling PJ; Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, VIC, Australia.; Department of Paediatrics, University of Melbourne, The Royal Children's Hospital, Melbourne, VIC, Australia., North KN; Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, VIC, Australia. kathryn.north@mcri.edu.au.; Department of Paediatrics, University of Melbourne, The Royal Children's Hospital, Melbourne, VIC, Australia.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2021 Jul 02; Vol. 7 (27). Date of Electronic Publication: 2021 Jul 02 (Print Publication: 2021).
DOI:	10.1126/sciadv.abg0088
Abstrakt:	Homozygosity for the common ACTN3 null polymorphism ( ACTN3 577X) results in α-actinin-3 deficiency in ~20% of humans worldwide and is linked to reduced sprint and power performance in both elite athletes and the general population. α-Actinin-3 deficiency is also associated with reduced muscle mass, increased risk of sarcopenia, and altered muscle wasting response induced by denervation and immobilization. Here, we show that α-actinin-3 plays a key role in the regulation of protein synthesis and breakdown signaling in skeletal muscle and influences muscle mass from early postnatal development. We also show that α-actinin-3 deficiency reduces the atrophic and anti-inflammatory response to the glucocorticoid dexamethasone in muscle and protects against dexamethasone-induced muscle wasting in female but not male mice. The effects of α-actinin-3 deficiency on muscle mass regulation and response to muscle wasting provide an additional mechanistic explanation for the positive selection of the ACTN3 577X allele in recent human history. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
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