Scientific article
Open access

Evidence for serpinB2-independent protection from TNF-alpha-induced apoptosis

Published inExperimental cell research, vol. 312, no. 3, p. 350-361
Publication date2006

Clade B serine proteinase inhibitors (serpins) are intracellular proteins, whereas most of their identified targets are extracellular. A proposed intracellular role for these inhibitors is protection from apoptosis. We investigated the contribution of serpinB2 (plasminogen activator inhibitor-2, PAI-2) activity in TNF-alpha-induced apoptosis. PAI-2 is expressed in many normal and transformed cell types, particularly after stimulation with inflammatory cytokines. PAI-2 has been linked to protection from TNF-alpha-induced apoptosis, and a stabilizing interaction with the retinoblastoma protein (Rb1) has been proposed. We examined the activity of PAI-2 in TNF-alpha-induced apoptosis using HeLa, Isreco-1 and HT1080 cell lines. Stimulation with TNF-alpha protected each cell type from apoptosis induced by TNF-alpha and cycloheximide. Protection correlated with an increase in PAI-2 expression in IS-1 and HT1080 cells but not in HeLa cells where PAI-2 mRNA and protein were undetectable. PAI-2 was overexpressed in each cell type but gave no protection from TNF-alpha-induced apoptosis measured by cell viability, annexinV binding and caspase-3/7 activity. We detected wild-type Rb1, unchanged TNF receptor levels and induction of other apoptosis-protective factors in all cell types. In conclusion, elevated PAI-2 levels do not protect cells from TNF-alpha-induced apoptosis, and the protective effect of prior stimulation with TNF-alpha does not require PAI-2.

  • Adaptor Proteins, Signal Transducing
  • Annexin A5/metabolism
  • Apoptosis/drug effects
  • Blotting, Western
  • Caspases/metabolism
  • Cell Proliferation/drug effects
  • Colonic Neoplasms/drug therapy/metabolism
  • Cycloheximide/pharmacology
  • DNA-Binding Proteins
  • Fibrosarcoma/drug therapy/metabolism
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lentivirus/genetics
  • Mutagenesis, Site-Directed
  • Mutation/genetics
  • Nuclear Proteins
  • Plasminogen Activator Inhibitor 2/genetics/metabolism
  • Protein Synthesis Inhibitors/pharmacology
  • Proteins/metabolism
  • Receptors, Tumor Necrosis Factor, Type I/metabolism
  • Retinoblastoma Protein/metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors/metabolism
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha/pharmacology
Citation (ISO format)
FISH, Richard, KRUITHOF, Egbert. Evidence for serpinB2-independent protection from TNF-alpha-induced apoptosis. In: Experimental cell research, 2006, vol. 312, n° 3, p. 350–361. doi: 10.1016/j.yexcr.2005.11.003
Main files (1)
Article (Published version)
ISSN of the journal0014-4827

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