Targeting GSK3 to attenuate spaceflight-induced SERCA dysfunction: Lessons from hindlimb-suspended mice

IF 4.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-01-27 DOI:10.1016/j.bbadis.2025.167694
Amélie A.T. Marais, Ryan W. Baranowski, Jessica L. Braun, Briana L. Hockey, Val A. Fajardo
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Abstract

  • In the absence of gravity, muscles become unloaded, reducing their size, strength, and endurance.
  • Calcium (Ca2+) dysregulation due to impairments in sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) function may be one reason for the decline in muscle performance.
  • Our previous work has shown that genetic reduction of glycogen synthase kinase 3 (GSK3) maintains soleus muscle mass and strength in mice after 7 days of hindlimb suspension.
  • Here, we tested whether these benefits could be, in part, due to an improvement in SERCA activity.
  • We show that muscle-specific GSK3 knockdown enhances soleus maximal SERCA activity, SERCA1 protein content, soleus relaxation and soleus muscle endurance.
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以 GSK3 为靶点减轻太空飞行诱发的 SERCA 功能障碍:后肢悬空小鼠的启示
•在没有重力的情况下,肌肉变得松弛,减少了它们的大小、力量和耐力。•肌内质网Ca2+- atp酶(SERCA)功能受损引起的钙(Ca2+)失调可能是肌肉性能下降的一个原因。•我们之前的工作表明,糖原合成酶激酶3 (GSK3)的遗传减少在小鼠后肢悬吊7天后维持比目鱼肌的质量和力量。•在这里,我们测试了这些益处是否部分是由于SERCA活性的改善。•研究表明,肌肉特异性GSK3敲低可增强比目鱼肌最大SERCA活性、SERCA1蛋白含量、比目鱼松弛和比目鱼肌耐力。
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来源期刊
CiteScore
12.30
自引率
0.00%
发文量
218
审稿时长
32 days
期刊介绍: BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.
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