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Biochem Biophys Res Commun. 2000 Apr 29;271(1):257-67.

The differential expression of apoptosis factors in the alveolar epithelium is redox sensitive and requires NF-kappaB (RelA)-selective targeting.

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Oxygen Signaling Group, University of Dundee, Dundee, Scotland, DD1 9SY, United Kingdom.


Fetal alveolar type II (fATII) epithelial cells were used to evaluate the role of signaling factors involved in oxidative stress-induced programmed cell death (PCD; apoptosis). Bcl-2, an antiapoptotic proto-oncogene, showed maximum abundance in hypoxia and mild reoxygenation, but declined thereafter. The Bcl-2 counterpart, Bax, which promotes PCD, displayed an increasing logarithmic profile with ascending DeltapO(2) regimen, such that the ratio of Bcl-2/Bax decreased as pO(2) increased. The expression of p53, a cell cycle regulator, paralleled Bax abundance. Pretreatment of fATII cells with l-buthionine-(S,R)-sulfoximine, an irreversible inhibitor of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in the biosynthesis of glutathione (GSH), enhanced Bax and p53 expression over Bcl-2. The GSH analogue, gamma-glutamylcysteinyl-ethyl ester, down-regulated Bax/p53 abundance but restored 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, whereas pyrrolidine dithiocarbamate induced Bax against Bcl-2, with mild effect on p53. Sulfasalazine, a potent and specific inhibitor of NF-kappaB, induced Bax at the expense of Bcl-2, in a p53-dependent manner. We conclude that 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-kappaB.

[Indexed for MEDLINE]

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