Jje. Haddad et Sc. Land, The differential expression of apoptosis factors in the alveolar epithelium is redox sensitive and requires NF-kappa B (RelA)-selective targeting, BIOC BIOP R, 271(1), 2000, pp. 257-267
Citations number
45
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Fetal alveolar type II (fATII) epithelial cells were used to evaluate the r
ole of signaling factors involved in oxidative stress-induced programmed ce
ll death (PCD; apoptosis). Bcl-2, an antiapoptotic proto-oncogene, showed m
aximum abundance in hypoxia and mild reoxygenation, but declined thereafter
. The Bcl-2 counterpart, Bax, which promotes PCD, displayed an increasing l
ogarithmic profile with ascending Delta pO(2) regimen, such that the ratio
of Bcl-2/Bax decreased as pO(2) increased. The expression of p53, a cell cy
cle regulator, paralleled Bax abundance. Pretreatment of fATII cells with L
-buthionine-(S,R)-sulfoximine, an irreversible inhibitor of gamma-glutamylc
ysteine synthetase, the rate-limiting enzyme in the biosynthesis of glutath
ione (GSH), enhanced Bax and p53 expression over Bcl-2. The GSH analogue, g
amma-glutamylcysteinyl-ethyl ester, down-regulated Bax/p53 abundance but re
stored that of Bcl-2, thereby increasing Bcl-2/Bax. The antioxidant and GSH
precursor N-acetyl-L-cysteine favored Bcl-2 at the expense of Bax/p53, whe
reas pyrrolidine dithiocarbamate induced Bax against Bcl-2, with mild effec
t on p53. Sulfasalazine, a potent and specific inhibitor of NF-kappa B, ind
uced Bax at the expense of Bcl-2, in a p53-dependent manner. We conclude th
at the differential expression of signaling factors involved in PCD in the
alveolar epithelium is redox-sensitive and mediated, at least in part, by a
negative feedback mechanism transduced by NF-kappa B. (C) 2000 Academic Pr
ess.