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首页> 外文期刊>Journal of Cellular Physiology >SIRT1 regulates nuclear number and domain size in skeletal muscle fibers
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SIRT1 regulates nuclear number and domain size in skeletal muscle fibers

机译:SIRT1调节核数量和域大小骨骼肌纤维

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Skeletal muscle fibers are giant multinucleated cells wherein individual nuclei govern the protein synthesis in a finite volume of cytoplasm; this is termed the myonuclear domain (MND). The factors that control MND size remain to be defined. In the present study, we studied the contribution of the NAD + ‐dependent deacetylase, sirtuin 1 (SIRT1), to the regulation of nuclear number and MND size. For this, we isolated myofibers from mice with tissue‐specific inactivation (mKO) or inducible overexpression (imOX) of SIRT1 and analyzed the 3D organisation of myonuclei. In imOX mice, the number of nuclei was increased whilst the average MND size was decreased as compared to littermate controls. Our findings were the opposite in mKO mice. Muscle stem cell (satellite cell) numbers were reduced in mKO muscles, a possible explanation for the lower density of myonuclei in these mice; however, no change was observed in imOX mice, suggesting that other factors might also be involved, such as the functional regulation of stem cells/muscle precursors. Interestingly, however, the changes in the MND volume did not impact the force‐generating capacity of muscle fibers. Taken together, our results demonstrate that SIRT1 is a key regulator of MND sizes, although the underlying molecular mechanisms and the cause‐effect relationship between MND and muscle function remain to be fully defined.
机译:骨骼肌纤维巨大的多核细胞中单个核控制蛋白质合成的有限体积细胞质;(MND)。定义。的贡献NAD +依赖性脱乙酰酶,sirtuin蛋白1 (SIRT1)的监管核数量和MND的大小。从小鼠组织地理隔离的肌纤维失活(营销)或诱导超表达(imOX) SIRT1和分析3 d组织myonuclei。同时提高MND的平均尺寸是什么减少与同窝出生仔畜控制。发现相反的在营销老鼠。干细胞(卫星细胞)的人数减少了在营销的肌肉,一个可能的解释在这些老鼠低密度myonuclei;然而,没有观察到变化imOX老鼠,这表明其他因素也可能涉及,如功能性监管干细胞/肌肉前体细胞。然而,MND体积的变化没有影响发电量等肌肉的力量纤维。SIRT1 MND大小的主要监管机构,尽管潜在的分子机制地理原因影响MND和之间的关系肌肉功能仍有待定义。

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