title: Senescence-related functional nuclear barrier by down-regulation of nucleo-cytoplasmic trafficking gene expression.
abstract: 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.
authors.affiliation: 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.
authors.forename: Sung Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Ryu
authors.forename: Hong Ju
authors.initials: HJ
authors.lastname: Ahn
authors.forename: Hae Ri
authors.initials: HR
authors.lastname: Choi
authors.forename: Hyun Tae
authors.initials: HT
authors.lastname: Kang
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Park
mesh_terms: 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