Compromised store-operated Ca2+ entry in aged skeletal muscle.

Compromised store-operated Ca2+ entry in aged skeletal muscle.
复制标题

衰老骨骼肌中钙池操纵的 Ca2+ 进入受损。

DOI:
10.1111/j.1474-9726.2008.00408.x
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发表时间:
2008-08
期刊:
影响因子:
7.8
通讯作者:
Brotto, Marco
Brotto, Marco
中科院分区:
生物学1区
文献类型:
--
作者:
Zhao, Xiaoli;Weisleder, Noah;Thornton, Angela;Oppong, Yaa;Campbell, Rachel;Ma, Jianjie;Brotto, Marco

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在衰老的骨骼肌中,收缩机制的组成和功能的变化不能完全解释观察到的收缩机制产生的比力的下降,而收缩机制是衰老过程中肌肉无力的特征。由于最近发现了老年非兴奋性和兴奋性细胞的细胞外 Ca2+ 内流的修饰,我们评估了老年小鼠骨骼肌中钙库操纵的 Ca2+ 内流 (SOCE) 的功能状态。使用 Fura-2 荧光的 Mn2+ 猝灭和横向小管 Ca2+ 运动的共焦显微成像,我们确定与年轻小鼠(2-5 个月)分离的肌肉纤维相比,老年小鼠(26-27 个月)分离的肌肉纤维中 SOCE 严重受损。虽然衰老骨骼肌中 SOCE 的降低似乎并不是由于 STIM1 表达水平改变或 Orai mRNA 表达降低所致,但这种 SOCE 的降低反映在从 mitsugumin-29 缺失的年轻小鼠中分离出的纤维中,mitsugumin-29 是一种突触素相关蛋白,在衰老骨骼肌中表现出表达降低。我们的数据表明,mitsugumin-29 表达的减少和 SOCE 的减少可能导致细胞内 Ca2+ 稳态能力的降低,通常与肌肉衰老相关。
In aged skeletal muscle, changes to the composition and function of the contractile machinery cannot fully explain the observed decrease in the specific force produced by the contractile machinery that characterizes muscle weakness during aging. Since modification in extracellular Ca2+ entry in aged nonexcitable and excitable cells has been recently identified, we evaluated the functional status of store-operated Ca2+ entry (SOCE) in aged mouse skeletal muscle. Using Mn2+ quenching of Fura-2 fluorescence and confocal-microscopic imaging of Ca2+ movement from the transverse tubules, we determined that SOCE was severely compromised in muscle fibers isolated from aged mice (26–27 months) as compared with those from young (2–5 months) mice. While reduced SOCE in aged skeletal muscle does not appear to result from altered expression levels of STIM1 or reduced expression of mRNA for Orai, this reduction in SOCE is mirrored in fibers isolated from young mice null for mitsugumin-29, a synaptophysin-related protein that displays decreased expression in aged skeletal muscle. Our data suggest that decreased mitsugumin-29 expression and reduced SOCE may contribute to the diminished intracellular Ca2+ homeostatic capacity generally associated with muscle aging.
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