Senescence-related functional nuclear barrier by down-regulation of nucleo-cytoplasmic trafficking gene expression.
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 hypo-responsiveness, 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.
Kim
Sung Young
SY
Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Institute on Aging, Seoul National University College of Medicine, Seoul 110-799, South Korea.
Ryu
Sung Jin
SJ
Ahn
Hong Ju
HJ
Choi
Hae Ri
HR
Kang
Hyun Tae
HT
Park
Sang Chul
SC
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism*; D004171:Diploidy; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D022022:Nuclear Pore / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis