Back to Search
Start Over
The differential expression of apoptosis factors in the alveolar epithelium is redox sensitive and requires NF-kappaB (RelA)-selective targeting.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2000 Apr 29; Vol. 271 (1), pp. 257-67. - Publication Year :
- 2000
-
Abstract
- 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.<br /> (Copyright 2000 Academic Press.)
- Subjects :
- Acetylcysteine pharmacology
Antioxidants pharmacology
Blotting, Western
Buthionine Sulfoximine pharmacology
DNA Fragmentation
Dipeptides pharmacology
Enzyme Inhibitors pharmacology
Epithelium metabolism
Free Radical Scavengers pharmacology
Glutathione antagonists & inhibitors
Glutathione biosynthesis
L-Lactate Dehydrogenase metabolism
Models, Biological
Oxygen metabolism
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins c-bcl-2 metabolism
Pyrrolidines pharmacology
Sulfasalazine pharmacology
Thiocarbamates pharmacology
bcl-2-Associated X Protein
Apoptosis
NF-kappa B metabolism
Oxidation-Reduction
Pulmonary Alveoli metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 271
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 10777712
- Full Text :
- https://doi.org/10.1006/bbrc.2000.2607