Plasminogen activator inhibitor type 2 inhibits tumor necrosis factor alpha-induced apoptosis. Evidence for an alternate biological function
| Autor: | J L, Dickinson, E J, Bates, A, Ferrante, T M, Antalis |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Cell Nucleus
Chloramphenicol O-Acetyltransferase Base Sequence Dose-Response Relationship Drug Cell Survival Tumor Necrosis Factor-alpha Immune Sera Immunoblotting Molecular Sequence Data Apoptosis Transfection Polymerase Chain Reaction Recombinant Proteins Cell Line Kinetics Mutagenesis Site-Directed Plasminogen Activator Inhibitor 2 Humans Point Mutation Amino Acid Sequence Cycloheximide DNA Primers HeLa Cells |
| Zdroj: | The Journal of biological chemistry. 270(46) |
| ISSN: | 0021-9258 |
| Popis: | Plasminogen activator inhibitor type 2 (PAI-2) is a serine proteinase inhibitor or serpin that is a major product of macrophages in response to endotoxin and inflammatory cytokines. We have explored the role of PAI-2 in apoptotic cell death initiated by tumor necrosis factor alpha (TNF). HeLa cells stably transfected with PAI-2 cDNA were protected from TNF-induced apoptosis, whereas cells transfected with antisense PAI-2 cDNA, a control gene, or the plasmid vector alone remained susceptible. The level of PAI-2 expressed by different HeLa cell clones was inversely correlated with their sensitivity to TNF. Loss of TNF sensitivity was not a result of loss of TNF receptor binding. In contrast, PAI-2 expression did not confer protection against apoptosis induced by ultraviolet or ionizing radiation. The serine proteinase urokinase-type plasminogen activator was not demonstrated to be the target of PAI-2 action. The P1-Arg amino acid residue of PAI-2 was determined to be required for protection, because cells expressing PAI-2 with an Ala in this position were not protected from TNF-mediated cell death. The results suggest that intracellular PAI-2 might be an important factor in regulating cell death in TNF-mediated inflammatory processes through inhibition of a proteinase involved in TNF-induced apoptosis. |
| Databáze: | OpenAIRE |
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