Age-related reductions in expression of serum response factor and myocardin-related transcription factor A in mouse skeletal muscles

Age-related reductions in expression of serum response factor and myocardin-related transcription factor A in mouse skeletal muscles
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DOI:
10.1016/j.bbadis.2008.03.008
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发表时间:
2008-07-01
影响因子:
6.2
通讯作者:
Yasuhara, Masahiro
Yasuhara, Masahiro
中科院分区:
生物学2区
文献类型:
--
作者:
Sakuma, Kunihiro;Akiho, Mai;Yasuhara, Masahiro

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在衰老过程中连接骨骼肌萎缩的分子信号通路尚未确定。使用逆转录(RT)-PCR,蛋白质印迹和免疫荧光显微镜,我们调查是否RhoA,RhoGDI,SRF,MRTF-A,和MyoD在肱三头肌和四头肌肌肉的量随年龄的变化在小鼠。使用年轻成年(3个月)和老年(24个月)C57 BL/6 J小鼠。衰老小鼠的股四头肌中有许多具有中央核的纤维。使用全肌匀浆或胞浆组分的蛋白质印迹法清楚地表明,SRF蛋白的量在老年骨骼肌中显著降低。免疫荧光标记表明,更多的SRF阳性肌纤维在年轻的小鼠。年轻和老年小鼠具有SRF免疫反应性在一些卫星细胞表达Pax 7。MRTF-A和STARS mRNA水平在肱三头肌和股四头肌中随着年龄的增长而显著下降。MRTF-A蛋白在衰老小鼠肌肉细胞核中的表达量明显减少。RhoA和RhoGDI在粗匀浆或细胞溶质和膜组分的量更大,在老年肌肉。衰老小鼠在细胞质和细胞核中具有显著较高水平的MyoD蛋白。SRF和MRTF表达的降低可能导致骨骼肌随增龄而萎缩。(C)2008 Elsevier B. V.保留所有权利。
The molecular signaling pathways linking the atrophy of skeletal muscle during aging have not been identified. Using reverse transcription (RT)-PCR, Western blotting, and immunofluorescence microscopy, we investigated whether the amounts of RhoA, RhoGDI, SRF, MRTF-A, and MyoD in the triceps brachii and quadriceps muscles change with aging in mice. Young adult (3 mo) and aged (24 mo) C57BL/6J mice were used. Senescent mice possessed many fibers with central nuclei in the quadriceps muscle. Western blotting using a homogenate of whole muscle or the cytosolic fraction clearly showed that the amount of SRF protein was significantly decreased in the aged skeletal muscles. Immunofluorescence labeling indicated more SRF-positive muscle fibers in young mice. Both young and old mice possessed SRF immunoreactivity in some satellite cells expressing Pax7. MRTF-A and STARS mRNA levels significantly declined with aging in the triceps brachii and quadriceps muscles. The amount of MRTF-A protein was markedly reduced in the nuclear fraction of aged muscle of mice. The amounts of RhoA and RhoGDI in the crude homogenate or the cytosolic and membrane fractions were greater in the aged muscle. Senescent mice possessed significantly higher levels of MyoD protein in the cytosol and nucleus. Decreased SRF and MRTF expression may induce the atrophy of skeletal muscle with aging. (C) 2008 Elsevier B.V. All rights reserved.