A Role for Caspase-1 in Serum Withdrawal-Induced Apoptosis of Endothelial Cells

Abstract

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.