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GSH‐dependent regulation of Fas‐mediated caspase‐8 activation by acrolein
Author(s) -
Hristova Milena,
Heuvelmans Sjanneke,
van der Vliet Albert
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.12.040
Subject(s) - acrolein , glutathione , buthionine sulfoximine , chemistry , cysteine , apoptosis , caspase , caspase 3 , jurkat cells , thiol , biochemistry , cysteine protease , microbiology and biotechnology , programmed cell death , biology , enzyme , immunology , t cell , immune system , catalysis
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 μM) 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.