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Plasminogen activator inhibitor type 2 inhibits tumour necrosis factor alpha-induced apoptosis. Evidence for an alternate biological function

Citation

Dickinson, JL and Bates, EJ and Ferrante, A and Antalis, TM, Plasminogen activator inhibitor type 2 inhibits tumour necrosis factor alpha-induced apoptosis. Evidence for an alternate biological function, Journal of Biological Chemistry, 270, (46) pp. 27894-27904. ISSN 0021-9258 (1995) [Refereed Article]

DOI: doi:10.1074/jbc.270.46.27894

Abstract

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 a (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 P 1 -Arg amine 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 he an important factor in regulating cell death in TNF-mediated inflammatory processes through inhibition of a proteinase involved in TNF-induced apoptosis.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Oncology and Carcinogenesis not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Dickinson, JL (Associate Professor Joanne Dickinson)
ID Code:35274
Year Published:1995
Web of Science® Times Cited:201
Deposited By:Menzies Centre
Deposited On:2005-08-04
Last Modified:2005-08-04
Downloads:0

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