Differential regulation of Shc adaptor proteins in skeletal muscle, spinal cord and forebrain of aged rats with sensorimotor impairment
Differential regulation of Shc adaptor proteins in skeletal muscle, spinal cord and forebrain of aged rats with sensorimotor impairment
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DOI：
10.1046/j.1474-9728.2003.00030.x
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发表时间：
2003-02-01
期刊：
影响因子：
7.8
通讯作者：
Ulfhake, B
中科院分区：
文献类型：
--
作者：
Jiang, XG;Edstrom, E;Ulfhake, B
Shc家族蛋白通过结合受体酪氨酸激酶参与有丝分裂和生存信号传导。我们在此报道了30月龄大鼠不同程度感觉运动损伤的前脑、脊髓和后肢肌肉中Shc的表达。ShcA （mRNA和蛋白）在老年大鼠骨骼肌和脊髓中上调，这种变化与生物年龄（即行为丧失能力的程度）有关，而与实足年龄无关。Western blot和RT-PCR显示，ShcA的增加选择性地影响脊髓中的p46亚型，而在肌肉组织中p66（ShcA）的强劲增加也很明显。此外，在ShcA上调的同时，老龄动物的p75(NTR) mRNA也增加。ShcB mRNA在脊髓和骨骼肌中均有下调的趋势，而ShcC的表达不变。我们的数据表明，Shc mrna在衰老过程中的调控是区域特异性的，也是同工异构体特异性的。这种调节变化可能反映了由年龄相关的细胞和组织损伤引起的有丝分裂/生存信号的变化。p66（ShcA）和p75（NTR）的偶联调控是有趣的，因为这两个分子都与细胞凋亡有关。
The Shc family of proteins participates in mitogenic and survival signalling through binding to receptor tyrosine kinases. We report here on the expression of Shc in fore-brain, spinal cord and hind limb muscles from 30-month-old rats with different degrees of sensorimotor impairment. ShcA (mRNA and protein) is up-regulated in skeletal muscles and spinal cord of aged rats, and this change relates to biological age, i.e. degree of behavioural incapacitation, rather than to chronological age. Western blot and RT-PCR revealed that the increase in ShcA selectively affected the p46 isoform in the spinal cord, whereas in muscle tissue a robust increase of p66(ShcA) was also evident. Furthermore, in parallel with the up-regulation of ShcA, an increase of p75(NTR) mRNA in the aged animals was observed. ShcB mRNA showed a tendency for down-regulation in both spinal cord and skeletal muscles, whereas the expression of ShcC was unaltered. Our data show that the regulation of Shc mRNAs in senescence is region as well as isoform specific. The regulatory changes may reflect changes in mitogenic/survival signalling induced by age-related cell and tissue damage. The coup-regulation of p66(ShcA) and p75(NTR) is interesting since both molecules have been associated with apoptosis.