A role for caspase-1 in serum withdrawal-induced apoptosis of endothelial cells

King, Andrea R., Francis, Sheila E., Bridgeman, Collette J., Bird, Helen, Whyte, Moira K. B. and Crossman, David C. (2003) A role for caspase-1 in serum withdrawal-induced apoptosis of endothelial cells. Laboratory Investigation, 83 (10). pp. 1497-1508. ISSN 0023-6837

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Mouse lung endothelial cells (MLEC) and HUVEC were used under serum withdrawal (SW) conditions as a model of endothelial cell (EC) apoptosis. Apoptosis was quantified by time-lapse video microscopy. Mouse lung ECs from caspase-1(-/-) mice had significantly reduced rates of SW-induced apoptosis compared with wild-type mice, specifically implicating caspase-1 in proapoptotic signaling in ECs. SW conditions induced HUVEC apoptosis with concomitant activation of caspase-1. Further studies demonstrated that the caspase-1 inhibitors z-VAD and z-YVAD significantly reduced the rate of SW-induced HUVEC apoptosis. HUVEC, when transfected with caspase-1, showed a highly significant increase in apoptosis. SW was associated with increases in reactive oxygen species production that were significantly inhibited by the antioxidant N-acetyl-L-cysteine, although rates of apoptosis and caspase-1 activation were unaffected. These results demonstrate the involvement of caspase-1 in SW-induced EC apoptosis, independently of reactive oxygen species production.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit
Depositing User: Rhiannon Harvey
Date Deposited: 17 May 2011 15:18
Last Modified: 16 Jan 2024 01:23
URI: https://ueaeprints.uea.ac.uk/id/eprint/30692
DOI: 10.1097/01.LAB.0000093096.62765.85

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