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gamma-Glutamyl transpeptidase is increased by oxidative stress in rat alveolar L2 epithelial cells.
Am J Respir Cell Mol Biol 1994; 11(5):586-92AJ

Abstract

The tripeptide glutathione (GSH) is used by cells to detoxify hydroperoxides, produced during oxidative stress, and is consumed in the process. Previous studies have indicated that cells can be protected against oxidative stress by extracellular GSH through its degradation catalyzed by the exoenzyme gamma-glutamyl transpeptidase (gamma GT) and its de novo synthesis within the cytosol. We hypothesized that gamma GT would be increased as part of the adaptation of cells to oxidative stress. We examined whether oxidative stress could increase gamma GT activity, protein, and mRNA in a lung epithelial cell line (L2). Cultures were subjected to H2O2-mediated toxicity by 15 min of exposure to the redox cycling quinone, menadione. Menadione (50 microM) caused an initial decrease (27 +/- 9% of baseline after 15 min) in intracellular GSH, followed by resynthesis to levels significantly higher than baseline (335 +/- 40% after 24 h, P < 0.001). This elevation was prevented by acivicin, a gamma GT inhibitor. Menadione also caused a dose-dependent increase in gamma GT enzymatic activity (715 +/- 125% of control at 24 h after 15 min of exposure to 100 microM menadione, P < 0.001) that was prevented by actinomycin D. Western blot analysis indicated increased levels of gamma GT protein with increasing menadione. A concentration-dependent increase in gamma GT-mRNA was also observed. Previous investigation has demonstrated that an increase in gamma GT activity enhances the capacity of cells to utilize extracellular GSH. The findings presented here are consistent with a role for gamma GT in cellular adaptation to oxidative stress.

Authors+Show Affiliations

Department of Pediatrics, Childrens Hospital Los Angeles, California.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

7946387

Citation

Kugelman, A, et al. "Gamma-Glutamyl Transpeptidase Is Increased By Oxidative Stress in Rat Alveolar L2 Epithelial Cells." American Journal of Respiratory Cell and Molecular Biology, vol. 11, no. 5, 1994, pp. 586-92.
Kugelman A, Choy HA, Liu R, et al. Gamma-Glutamyl transpeptidase is increased by oxidative stress in rat alveolar L2 epithelial cells. Am J Respir Cell Mol Biol. 1994;11(5):586-92.
Kugelman, A., Choy, H. A., Liu, R., Shi, M. M., Gozal, E., & Forman, H. J. (1994). Gamma-Glutamyl transpeptidase is increased by oxidative stress in rat alveolar L2 epithelial cells. American Journal of Respiratory Cell and Molecular Biology, 11(5), pp. 586-92.
Kugelman A, et al. Gamma-Glutamyl Transpeptidase Is Increased By Oxidative Stress in Rat Alveolar L2 Epithelial Cells. Am J Respir Cell Mol Biol. 1994;11(5):586-92. PubMed PMID: 7946387.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - gamma-Glutamyl transpeptidase is increased by oxidative stress in rat alveolar L2 epithelial cells. AU - Kugelman,A, AU - Choy,H A, AU - Liu,R, AU - Shi,M M, AU - Gozal,E, AU - Forman,H J, PY - 1994/11/1/pubmed PY - 1994/11/1/medline PY - 1994/11/1/entrez SP - 586 EP - 92 JF - American journal of respiratory cell and molecular biology JO - Am. J. Respir. Cell Mol. Biol. VL - 11 IS - 5 N2 - The tripeptide glutathione (GSH) is used by cells to detoxify hydroperoxides, produced during oxidative stress, and is consumed in the process. Previous studies have indicated that cells can be protected against oxidative stress by extracellular GSH through its degradation catalyzed by the exoenzyme gamma-glutamyl transpeptidase (gamma GT) and its de novo synthesis within the cytosol. We hypothesized that gamma GT would be increased as part of the adaptation of cells to oxidative stress. We examined whether oxidative stress could increase gamma GT activity, protein, and mRNA in a lung epithelial cell line (L2). Cultures were subjected to H2O2-mediated toxicity by 15 min of exposure to the redox cycling quinone, menadione. Menadione (50 microM) caused an initial decrease (27 +/- 9% of baseline after 15 min) in intracellular GSH, followed by resynthesis to levels significantly higher than baseline (335 +/- 40% after 24 h, P < 0.001). This elevation was prevented by acivicin, a gamma GT inhibitor. Menadione also caused a dose-dependent increase in gamma GT enzymatic activity (715 +/- 125% of control at 24 h after 15 min of exposure to 100 microM menadione, P < 0.001) that was prevented by actinomycin D. Western blot analysis indicated increased levels of gamma GT protein with increasing menadione. A concentration-dependent increase in gamma GT-mRNA was also observed. Previous investigation has demonstrated that an increase in gamma GT activity enhances the capacity of cells to utilize extracellular GSH. The findings presented here are consistent with a role for gamma GT in cellular adaptation to oxidative stress. SN - 1044-1549 UR - https://www.unboundmedicine.com/medline/citation/7946387/gamma_Glutamyl_transpeptidase_is_increased_by_oxidative_stress_in_rat_alveolar_L2_epithelial_cells_ L2 - http://www.atsjournals.org/doi/full/10.1165/ajrcmb.11.5.7946387?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -