GSH-dependent regulation of Fas-mediated caspase-8 activation by acrolein.
Activation of the cysteine protease caspase-8 by the death receptor Fas (CD95/APO-1) in B lymphoblastoid SKW6.4 cells or Jurkat T cells is associated with GSH depletion. Conversely, GSH depletion by the aldehyde acrolein (3-30 microM) was associated with inhibition of Fas-induced caspase-8 activation, although GSH depletion by buthionine sulfoximine (BSO) did not affect caspase-8 activation. In contrast to BSO, acrolein caused a loss of caspase-8 cysteine content in association with direct alkylation of caspase-8. Our findings indicate that inhibition of caspase-8 by thiol-reactive agents such as acrolein is not due to GSH depletion but caused by direct protein thiol modifications.
Hristova
Milena
M
Department of Pathology, College of Medicine, University of Vermont, 89 Beaumont Avenue, Burlington, VT 05405, USA.
Heuvelmans
Sjanneke
S
van der Vliet
Albert
A
D000171:Acrolein / Q000494:pharmacology*; D000478:Alkylation; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D053181:Caspase 8 / Q000737:chemistry / Q000378:metabolism*; D061945:Caspase Inhibitors; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
D061945:Caspase Inhibitors; D019014:fas Receptor; D019328:Buthionine Sulfoximine; D000171:Acrolein; D053181:Caspase 8; D005978:Glutathione; D003545:Cysteine