Selenoprotein P deficiency protects against immobilization-induced muscle atrophy by suppressing atrophy-related E3 ubiquitin ligases
Selenoprotein P deficiency protects against immobilization-induced muscle atrophy by suppressing atrophy-related E3 ubiquitin ligases
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DOI：
10.1152/ajpendo.00270.2022
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发表时间：
2023-06-01
影响因子：
5.1
通讯作者：
Takamura，Toshinari
中科院分区：
文献类型：
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作者：
Abuduwaili，Halimulati;Kamoshita，Kyoko;Takamura，Toshinari
骨骼肌的质量是通过蛋白质生物合成和降解之间的平衡来维持的。这种平衡的破坏导致肌肉减少症。然而，其潜在的机制仍然研究不足。硒蛋白P（SeP;由Selenopin小鼠编码）是一种肝细胞因子，在2型糖尿病和衰老中上调，并通过还原性应激引起信号抵抗。我们建立了硒基因敲除（KO）小鼠肌肉萎缩模型。固定（IMM）显着减少了骨骼肌纤维的横截面积和尺寸，而KO小鼠的情况有所改善。IMM上调骨骼肌中编码E3泛素连接酶及其上游FoxO 1、FoxO 3和KLF 15转录因子的基因，而在KO小鼠中这些基因受到抑制。这些研究结果表明，SeP介导的还原性应激可能参与了身体失活介导的肌肉减少症，这可能是一个治疗靶点对sarcopenia.NEW & NOTEWORTHYSelenoprotein P（SeP）是一种肝细胞因子，在2型糖尿病和衰老中上调，并通过还原性应激引起信号阻力。固定（IMM）显着减少小鼠的骨骼肌质量，这是防止在SeP敲除（KO）小鼠。IMM诱导的Foxos/KLF 15-atrogene上调在KO小鼠的骨骼肌中被抑制。这些发现表明，SeP介导的还原性应激参与并可能是物理失活介导的肌肉萎缩的治疗靶点。
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 bySelenopin 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 inSelenopknockout (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 & NOTEWORTHYSelenoprotein 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.