SIRT1 regulates nuclear number and domain size in skeletal muscle fibers.
SIRT1 regulates nuclear number and domain size in skeletal muscle fibers.
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DOI：
10.1002/jcp.26542
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发表时间：
2018-09
影响因子：
5.6
通讯作者：
Ochala J
中科院分区：
文献类型：
--
作者：
Ross JA;Levy Y;Svensson K;Philp A;Schenk S;Ochala J
骨骼肌纤维是巨大的多核细胞，其中单个细胞核在有限体积的细胞质中控制蛋白质合成；这被称为mynuclear domain （MND）。控制MND大小的因素仍有待确定。在本研究中，我们研究了NAD+依赖性去乙酰化酶sirtuin 1 （SIRT1）对核数和MND大小的调节作用。为此，我们从SIRT1组织特异性失活（mKO）或诱导型过表达（imOX）小鼠中分离肌纤维，并分析了肌核的三维组织。在imOX小鼠中，与对照组相比，细胞核数量增加，而平均MND大小减小。我们的研究结果在mKO小鼠中正好相反。mKO肌肉中的肌肉干细胞（卫星细胞）数量减少，这可能解释了这些小鼠中肌核密度较低的原因；然而，在imOX小鼠中没有观察到变化，这表明其他因素也可能参与其中，例如干细胞/肌肉前体的功能调节。然而，有趣的是，MND体积的变化并没有影响肌纤维的发力能力。综上所述，我们的研究结果表明SIRT1是MND大小的关键调节因子，尽管MND与肌肉功能之间的潜在分子机制和因果关系仍有待完全确定。
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.
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影响因子：
5.5
作者：
Bruusgaard, JC;Liestol, K;Gundersen, K
通讯作者：
Gundersen, K
影响因子：
2.4
作者：
EDGERTON, VR;ROY, RR
通讯作者：
ROY, RR
DOI：
10.1097/nen.0b013e318293b1cc
发表时间：
2013-06-01
影响因子：
3.2
作者：
Lindqvist, Johan;Cheng, Arthur J.;Ochala, Julien
通讯作者：
Ochala, Julien
影响因子：
3.7
作者：
Ochala, Julien;Ravenscroft, Gianina;Nowak, Kristen J.
通讯作者：
Nowak, Kristen J.
影响因子：
4.8
作者：
Philp, Andrew;Chen, Ai;Schenk, Simon
通讯作者：
Schenk, Simon