Senescence-related functional nuclear barrier by down-regulation of nucleo-cytoplasmic trafficking gene expression
Senescence-related functional nuclear barrier by down-regulation of nucleo-cytoplasmic trafficking gene expression
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DOI：
10.1016/j.bbrc.2009.10.154
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发表时间：
2010-01-01
影响因子：
3.1
通讯作者：
Park, Sang Chul
中科院分区：
文献类型：
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作者：
Kim, Sung Young;Ryu, Sung Jin;Park, Sang Chul
衰老细胞的特征性性质之一是不仅对生长因子而且对凋亡应激的低反应性或无反应性。在本研究中，我们证实了在衰老的人二倍体成纤维细胞中，激活的p-ERK 1/2和NF-κ B p50的核转位响应于生长刺激或LPS的抑制。为了阐明衰老相关的低反应性的潜在机制，我们通过微阵列分析进行了基因表达谱的比较研究。因此，我们观察到，与年轻细胞相比，衰老细胞中的核质运输基因的表达大量减少，几种核孔蛋白的表达水平。通过RT-PCR和Western blot方法证实，在衰老的HDFs中，karyopherin alpha、karyopherin beta、Ran和Ran调节因子被下调。总之，这些数据表明，某些衰老相关的功能性核屏障的运作，通过下调核质运输基因在衰老细胞。(C)2009 Elsevier Inc. All rights reserved.
One of the characteristic natures of senescent cells is the hypo- or irresponsiveness not only to growth factors but also to apoptotic stress. In the present study, we confirmed the inhibition of nuclear translocation of activated p-ERK1/2 and NF-kB p50 in response to growth stimuli or LPS in the senescent human diploid fibroblasts. In order to elucidate the underlying mechanism for the senescence-associated hyporesponsiveness, we carried out the comparison study for gene expression profiles through microarray analysis. In consequence, we observed the vast reduction in expression of nucleo-cytoplasmic trafficking genes in senescent cells, when compared with those in young cells Expression levels of several nucleoporins. karyopherin alpha, karyopherin beta, Ran, and Ran-regulating factors were confirmed to be down-regulated in senescent HDFs by using RT-PCR and Western blot methods. Taken together, these data suggest the operation of certain senescence-associated functional nuclear barriers by down-regulation of the nucleo-cytoplasmic trafficking genes in the senescent cells. (C) 2009 Elsevier Inc. All rights reserved.