Selenoprotein P deficiency protects against immobilization-induced muscle atrophy by suppressing atrophy-related E3 ubiquitin ligases.

Autor:	Abuduwaili H; Department of Endocrinology and Metabolism, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Kamoshita K; Department of Endocrinology and Metabolism, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Ishii KA; Department of Endocrinology and Metabolism, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.; Department of Integrative Medicine for Longevity, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.; Department of Musculoskeletal Disease, National Center for Geriatrics and Gerontology (NCGG), Aichi, Japan., Takahashi K; Department of Human Pathology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Abuduyimiti T; Department of Endocrinology and Metabolism, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Qifang L; Department of Endocrinology and Metabolism, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Isobe Y; Department of Endocrinology and Metabolism, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Goto H; Department of Endocrinology and Metabolism, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Nakano Y; Department of Endocrinology and Metabolism, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Takeshita Y; Department of Endocrinology and Metabolism, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Takayama H; Department of Endocrinology and Metabolism, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.; Department of System Biology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Harada K; Department of Human Pathology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Takamura T; Department of Endocrinology and Metabolism, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2023 Jun 01; Vol. 324 (6), pp. E542-E552. Date of Electronic Publication: 2023 Mar 22.
DOI:	10.1152/ajpendo.00270.2022
Abstrakt:	The quality of skeletal muscle is maintained by a balance between protein biosynthesis and degradation. Disruption in this balance results in sarcopenia. However, its underlying mechanisms remain underinvestigated. Selenoprotein P (SeP; encoded by Selenop in mice) is a hepatokine that is upregulated in type 2 diabetes and aging and causes signal resistances via reductive stress. We created immobilized muscle atrophy model in Selenop knockout (KO) mice. Immobilization (IMM) significantly reduced cross-sectional areas and the size of skeletal muscle fibers, which were ameliorated in KO mice. IMM upregulated the genes encoding E3 ubiquitin ligases and their upstream FoxO1, FoxO3, and KLF15 transcription factors in the skeletal muscle, which were suppressed in KO mice. These findings suggest a possible involvement of SeP-mediated reductive stress in physical inactivity-mediated sarcopenia, which may be a therapeutic target against sarcopenia. NEW & NOTEWORTHY Selenoprotein P (SeP) is a hepatokine that is upregulated in type 2 diabetes and aging and causes signal resistances via reductive stress. Immobilization (IMM) significantly reduced skeletal muscle mass in mice, which was prevented in SeP knockout (KO) mice. IMM-induced Foxos/KLF15-atrogene upregulation was suppressed in the skeletal muscle of KO mice. These findings suggest that SeP-mediated reductive stress is involved in and may be a therapeutic target for physical inactivity-mediated muscle atrophy.
Databáze:	MEDLINE
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