Fas-mediated apoptosis of proliferating, transiently growth-arrested, and senescent normal human fibroblasts

Clifford G Tepper, Michael F Seldin, Maria Mudryj

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Previous studies suggest that apoptotic signaling may require proteins that are critical to cellular proliferation and cell cycle regulation. To further examine this question, proliferating, transiently growth-arrested, and senescent normal human fibroblasts were induced to undergo apoptosis in response to two distinct mediators of apoptosis - Fas (APO-1/CD95) death receptor and staurosporine. Ligation of the Fas receptor in the presence of cycloheximide or actinomycin D resulted in apoptosis of proliferating cells, cells transiently growth arrested by γ-irradiation or serum starvation (i.e., G0 arrest), and permanently growth-arrested senescent fibroblasts. Proliferating and G0-arrested cells were also susceptible to staurosporine-mediated apoptosis. Surprisingly, γ-irradiated cells did not undergo staurosporine-mediated apoptosis, and remained viable for a prolonged time. Fas-mediated apoptosis of senescent fibroblasts was evidenced by chromosome condensation and by activation of caspase-8 and -3, proteases crucial for the execution of the Fas apoptosis pathway. In addition, ligation of the Fas receptor in G0-arrested cells did not result in the activation of p34(cdc2) kinase, arguing that activation of this kinase is not essential in this apoptotic process. From these studies we conclude that proliferating, transiently growth-arrested, and senescent normal human fibroblasts are susceptible to apoptotic signals and that apoptosis is not necessarily dependent upon cell cycle or proliferative state of the cell. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)9-19
Number of pages11
JournalExperimental Cell Research
Volume260
Issue number1
DOIs
StatePublished - Oct 10 2000

Keywords

  • Apoptosis
  • Cell cycle
  • Fas
  • Irradiation
  • Senescence

ASJC Scopus subject areas

  • Cell Biology

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