A role for caspase-1 in serum withdrawal-induced apoptosis of endothelial cells.
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.
King
Andrea R
AR
Cardiovascular Research Group, Division of Clinical Sciences (North), Clinical Sciences Centre, University of Sheffield, Northern General Hospital, Sheffield, United Kingdom. a.r.king@sheffield.ac.uk
Francis
Sheila E
SE
Bridgeman
Collette J
CJ
Bird
Helen
H
Whyte
Moira K B
MK
Crossman
David C
DC
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D020170:Caspase 1 / Q000378:metabolism*; D061945:Caspase Inhibitors; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008168:Lung / Q000098:blood supply; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017382:Reactive Oxygen Species / Q000378:metabolism; D012501:Saphenous Vein / Q000166:cytology; D014471:Umbilical Veins / Q000166:cytology
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; C460579:benzyloxycarbonyltyrosyl-valyl-alanyl-aspartic acid fluoromethyl ketone; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D020170:Caspase 1