@article {3095182,
	title = {Ceramide-mediated apoptosis in lung epithelial cells is regulated by glutathione.},
	journal = {Am J Respir Cell Mol Biol},
	volume = {25},
	year = {2001},
	month = {2001 Dec},
	pages = {676-84},
	abstract = {Reactive oxygen species (ROS) are mediators of lung injury, and glutathione (GSH) is the major nonprotein antioxidant that protects the cell from oxidative stress. We have recently shown that H(2)O(2) induces ceramide-mediated apoptosis in human lung epithelial cells. We hypothesized that ROS-mediated depletion of GSH plays a regulatory role in ceramide generation, and thus in the induction of apoptosis. Our present studies demonstrate that GSH at physiologic concentrations (1 to 10 mM) inhibits ceramide production in a time- and dose-dependent manner in A549 human alveolar epithelial cells. On the other hand, buthionine-sulfoximine-mediated depletion of intracellular GSH induces elevation of ceramide levels and apoptosis. In addition, GSH blocks H(2)O(2)-mediated induction of intracellular ceramide generation and apoptosis. These effects were not mimicked by oxidized GSH (GSSG) or other thiol antioxidants, such as dithiothreitol and 2-mercaptoethanol. Moreover, increase of intracellular H(2)O(2), mediated by inhibition of catalase by aminotriazole, also induces ceramide generation and apoptosis. These effects were blocked by N-acetylcysteine. Our results suggest that GSH depletion may be the link between oxidative stress and ceramide-mediated apoptosis in the lung.},
	keywords = {Acetylcysteine, Amitrole, Annexin A5, antioxidants, Apoptosis, Bronchi, Buthionine Sulfoximine, Catalase, Cells, Cultured, Ceramides, Diacylglycerol Kinase, Dithiothreitol, DNA Fragmentation, Dose-Response Relationship, Drug, Enzyme Inhibitors, Epithelial Cells, Flow Cytometry, glutathione, Humans, Hydrogen Peroxide, In Situ Nick-End Labeling, Mercaptoethanol, Microscopy, Fluorescence, Oxidation-Reduction, Oxidative Stress, Pulmonary Alveoli, reactive oxygen species, Trachea},
	author = {Lavrentiadou, S N and Chan, C and Kawcak, T and Ravid, T and Tsaba, A and van der Vliet, A and Rasooly, R and Goldkorn, T}
}
