title: Nuclear accumulation of globular actin as a cellular senescence marker.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: In Hae
authors.initials: IH
authors.lastname: Kwak
authors.forename: Hong Seok
authors.initials: HS
authors.lastname: Kim
authors.forename: Ok Ran
authors.initials: OR
authors.lastname: Choi
authors.forename: Min Sook
authors.initials: MS
authors.lastname: Ryu
authors.forename: In Kyoung
authors.initials: IK
authors.lastname: Lim
mesh_terms: D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D003676:Deferoxamine / Q000494:pharmacology; D004171:Diploidy; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006918:Hydroxyurea / Q000494:pharmacology; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D008840:Microfilament Proteins; D006861:Hydrogen Peroxide; D003676:Deferoxamine; D006918:Hydroxyurea