Ceramide-mediated apoptosis in lung epithelial cells is regulated by glutathione

S. N. Lavrentiadou, C. Chan, Kawcak T'Nay Kawcak, T. Ravid, A. Tsaba, A. Van der Vliet, R. Rasooly, Tzipora Goldkorn

Research output: Contribution to journalArticle

92 Scopus citations

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 H2O2 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 H2O2-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 H2O2, 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.

Original languageEnglish (US)
Pages (from-to)676-684
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume25
Issue number6
StatePublished - 2001

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Fingerprint Dive into the research topics of 'Ceramide-mediated apoptosis in lung epithelial cells is regulated by glutathione'. Together they form a unique fingerprint.

  • Cite this

    Lavrentiadou, S. N., Chan, C., T'Nay Kawcak, K., Ravid, T., Tsaba, A., Van der Vliet, A., Rasooly, R., & Goldkorn, T. (2001). Ceramide-mediated apoptosis in lung epithelial cells is regulated by glutathione. American Journal of Respiratory Cell and Molecular Biology, 25(6), 676-684.