Stress-induced premature senescence in BJ and hTERT-BJ1 human foreskin fibroblasts.
To test the involvement of the telomeres in the senescent phenotype, we used telomerase-immortalized human foreskin fibroblasts (hTERT-BJ1). We exposed hTERT-BJ1 and parental BJ cells to either UVB or H(2)O(2) subcytotoxic stress(es). Both cell lines developed biomarkers of replicative senescence: loss of replicative potential, increase in senescence-associated beta-galactosidase activity, typical senescence-like morphology, overexpression of p21(WAF-1) and p16(INK-4a), and decreased level of the hyperphosphorylated form of pRb. Telomere shortening was slightly higher under stress for both BJ and hTERT-BJ1 but still much lower than that reported for other cell lines. We conclude that pathways alternative to telomere shortening must cause the appearance of the senescence phenotype.
Research Unit on Cellular Biology, Department of Biology, University of Namur (FUNDP), Rue de Bruxelles 61, 5000, Namur, Belgium.
João Pedro
JP
de Magalhães
Florence
F
Chainiaux
José
J
Remacle
Olivier
O
Toussaint
D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000032:analysis / Q000378:metabolism; D012867:Skin / Q000473:pathology; D013312:Stress, Physiological / Q000473:pathology*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide; D019098:Telomerase