Age-dependent changes in nuclear-cytoplasmic signaling in skeletal muscle.

Age-dependent changes in nuclear-cytoplasmic signaling in skeletal muscle.
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DOI:
10.1016/j.exger.2021.111338
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发表时间:
2021-07-15
影响因子:
3.9
通讯作者:
Lovering RM
Lovering RM
中科院分区:
医学2区
文献类型:
--
作者:
Iyer SR;Hsia RC;Folker ES;Lovering RM

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机械力通过肌纤维传导到细胞核中以调节肌肉发育、肥大和稳态。我们假设,在老年肌肉细胞核的核膜和相关蛋白质的变化,导致改变标记的机械信号。评价雅普/TAZ蛋白表达和下游靶点Ankrd 1和Cyr 61的基因表达作为机械转导指标。核板层和核孔复合体(NPC)中的蛋白质表达进行了评估,并通过电子显微镜观察核形态。通过摄取70 kDa荧光葡聚糖来评估核膜通透性。随着衰老,核变化包括核纤层蛋白β1和Nup 107的相对减少,以及Nup 93的相对增加,这可能是异常核形态、核泄漏增加和雅普/TAZ信号升高的基础。老年肌肉具有过度活跃的核-胞质信号传导,指示改变的核机械转导。这些数据突出了细胞核在衰老相关的异常机械感知中的可能作用。
Mechanical forces are conducted through myofibers and into nuclei to regulate muscle development, hypertrophy, and homeostasis. We hypothesized that nuclei in aged muscle have changes in the nuclear envelope and associated proteins, resulting in altered markers of mechano-signaling. YAP/TAZ protein expression and gene expression of downstream targets, Ankrd1 and Cyr61, were evaluated as mechanotransduction indicators. Expression of proteins in the nuclear lamina and the nuclear pore complex (NPC) were assessed, and nuclear morphology was characterized by electron microscopy. Nuclear envelope permeability was assessed by uptake of 70 kDa fluorescent dextran. Nuclear changes with aging included a relative decrease of lamin β1 and Nup107, and a relative increase in Nup93, which could underlie the aberrant nuclear morphology, increased nuclear leakiness, and elevated YAP/TAZ signaling. Aged muscles have hyperactive nuclear-cytoplasmic signaling, indicative of altered nuclear mechanotransduction. These data highlight a possible role for the nucleus in aging-related aberrant mechano-sensing.
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