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Nuclear accumulation of globular actin as a cellular senescence marker.

Authors
Kwak, IH; Kim, HS; Choi, OR; Ryu, MS; Lim, IK
Citation
Cancer research, 64(2):572-580, 2004
Journal Title
Cancer research
ISSN
0008-54721538-7445
Abstract
We evaluated the nuclear actin accumulation as a new marker of cellular senescence, using human diploid fibroblast (HDF), chondrocyte primary cultures, Mv1Lu epithelial cells, and Huh7 cancer cells. Nuclear accumulation of globular actin (G-actin) and dephosphorylated cofilin was highly significant in the senescent HDF cells, accompanied with inhibition of LIM kinase (LIMK) -1 activity. When nuclear export of the actin was induced by 12-O-tetradecanoylphorbol-13-acetate, DNA synthesis of the senescent cells increased significantly, accompanied with changes of morphologic and biochemical profiles, such as increased RB protein phosphorylation and decreased expressions of p21(WAF1), cytoplasmic p-extracellular signal-regulated kinase 1/2, and caveolins 1 and 2. Significance of these findings was strengthened additionally by the fact that nuclear actin export of young HDF cells was inhibited by the treatment with leptomycin B and mutant cofilin transfection, whose LIMK-1 phosphorylation site was lost, and the old cell phenotypes were duplicated with nuclear actin accumulation, suggesting that nuclear actin accumulation was accompanied with G1 arrest during cellular senescence. The aforementioned changes were observed not only in the replicative senescence but also in the senescence induced by treatment of HDF cells, Mv1Lu, primary culture of human chondrocytes, or Huh7 cells with H-ras virus infection, hydroxyurea, deferoxamine, or H(2)O(2). Nuclear actin accumulation was much more sensitive and an earlier event than the well-known, senescence-associated beta-galactosidase activity.
MeSH terms
Actin Depolymerizing FactorsActins/*metabolismCell Aging/drug effects/*physiologyCell Nucleus/drug effects/*physiologyCells, CulturedDeferoxamine/pharmacologyDiploidyFibroblasts/cytology/drug effects/physiologyHumansHydrogen Peroxide/pharmacologyHydroxyurea/pharmacologyImmunohistochemistryMicrofilament Proteins/metabolism
PMID
14744771
Appears in Collections:
Journal Papers > Research Organization > BK21
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
유, 민숙임, 인경
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