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Differential regulation of glutathione by oxidants and dexamethasone in alveolar epithelial cells.
Am J Physiol. 1998 07; 275(1):L80-6.AJ

Abstract

We studied the regulation of GSH and the enzymes involved in GSH regulation, gamma-glutamylcysteine synthetase (gamma-GCS) and gamma-glutamyl transpeptidase (gamma-GT), in response to the oxidants menadione, xanthine/xanthine oxidase, hyperoxia, and cigarette smoke condensate in human alveolar epithelial cells (A549). Menadione (100 microM), xanthine/xanthine oxidase (50 microM/10 mU), and cigarette smoke condensate (10%) exposure produced increased GSH levels (240 +/- 6, 202 +/- 12, and 191 +/- 2 nmol/mg protein, respectively; P < 0.001) compared with the control level (132 +/- 8 nmol/mg protein), which were associated with a significant increase in gamma-GCS activity (0.18 +/- 0.006, 0.16 +/- 0.01, and 0.17 +/- 0. 008 U/mg protein, respectively; P < 0.01) compared with the control level (0.08 +/- 0.001 U/mg protein) at 24 h. Exposure to hyperoxia (95% O2) resulted in a time-dependent increase in GSH levels. gamma-GCS activity increased significantly at 4 h (P < 0.001), returning to control values after 12 h of exposure. Dexamethasone (3 microM) exposure produced a significant time-dependent decrease in the levels of GSH and gamma-GCS activity at 24-96 h. The activity of gamma-GT did not change after oxidant treatment; however, it was decreased significantly by dexamethasone at 24-96 h. Thus oxidants and dexamethasone modulate GSH levels and activities of gamma-GT and gamma-GCS by different mechanisms. We suggest that the increase in gamma-GCS activity but not in gamma-GT activity may be required for the increase in intracellular GSH under oxidative stress in alveolar epithelial cells.

Authors+Show Affiliations

The Rayne Laboratory, Respiratory Medicine Unit, Department of Medicine, University of Edinburgh, Edinburgh EH8 9AG, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9688938

Citation

Rahman, I, et al. "Differential Regulation of Glutathione By Oxidants and Dexamethasone in Alveolar Epithelial Cells." The American Journal of Physiology, vol. 275, no. 1, 1998, pp. L80-6.
Rahman I, Bel A, Mulier B, et al. Differential regulation of glutathione by oxidants and dexamethasone in alveolar epithelial cells. Am J Physiol. 1998;275(1):L80-6.
Rahman, I., Bel, A., Mulier, B., Donaldson, K., & MacNee, W. (1998). Differential regulation of glutathione by oxidants and dexamethasone in alveolar epithelial cells. The American Journal of Physiology, 275(1), L80-6. https://doi.org/10.1152/ajplung.1998.275.1.L80
Rahman I, et al. Differential Regulation of Glutathione By Oxidants and Dexamethasone in Alveolar Epithelial Cells. Am J Physiol. 1998;275(1):L80-6. PubMed PMID: 9688938.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential regulation of glutathione by oxidants and dexamethasone in alveolar epithelial cells. AU - Rahman,I, AU - Bel,A, AU - Mulier,B, AU - Donaldson,K, AU - MacNee,W, PY - 1998/8/5/pubmed PY - 1998/8/5/medline PY - 1998/8/5/entrez SP - L80 EP - 6 JF - The American journal of physiology JO - Am. J. Physiol. VL - 275 IS - 1 N2 - We studied the regulation of GSH and the enzymes involved in GSH regulation, gamma-glutamylcysteine synthetase (gamma-GCS) and gamma-glutamyl transpeptidase (gamma-GT), in response to the oxidants menadione, xanthine/xanthine oxidase, hyperoxia, and cigarette smoke condensate in human alveolar epithelial cells (A549). Menadione (100 microM), xanthine/xanthine oxidase (50 microM/10 mU), and cigarette smoke condensate (10%) exposure produced increased GSH levels (240 +/- 6, 202 +/- 12, and 191 +/- 2 nmol/mg protein, respectively; P < 0.001) compared with the control level (132 +/- 8 nmol/mg protein), which were associated with a significant increase in gamma-GCS activity (0.18 +/- 0.006, 0.16 +/- 0.01, and 0.17 +/- 0. 008 U/mg protein, respectively; P < 0.01) compared with the control level (0.08 +/- 0.001 U/mg protein) at 24 h. Exposure to hyperoxia (95% O2) resulted in a time-dependent increase in GSH levels. gamma-GCS activity increased significantly at 4 h (P < 0.001), returning to control values after 12 h of exposure. Dexamethasone (3 microM) exposure produced a significant time-dependent decrease in the levels of GSH and gamma-GCS activity at 24-96 h. The activity of gamma-GT did not change after oxidant treatment; however, it was decreased significantly by dexamethasone at 24-96 h. Thus oxidants and dexamethasone modulate GSH levels and activities of gamma-GT and gamma-GCS by different mechanisms. We suggest that the increase in gamma-GCS activity but not in gamma-GT activity may be required for the increase in intracellular GSH under oxidative stress in alveolar epithelial cells. SN - 0002-9513 UR - https://www.unboundmedicine.com/medline/citation/9688938/Differential_regulation_of_glutathione_by_oxidants_and_dexamethasone_in_alveolar_epithelial_cells_ L2 - http://journals.physiology.org/doi/full/10.1152/ajplung.1998.275.1.L80?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -