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Differential enhancement of gamma-glutamyl transpeptidase and gamma-glutamylcysteine synthetase by tert-butylhydroquinone in rat lung epithelial L2 cells.
Am J Respir Cell Mol Biol 1996; 14(2):186-91AJ

Abstract

Sublethal quinone-mediated oxidative stress stimulates increases in the activities and mRNA levels of gamma-glutamyl transpeptidase (GGT) and gamma-glutamylcysteine synthetase (GCS) in rat lung epithelial L2 cells [Kugelman, A. et al. 1994. Am. J. Respir. Cell Mol. Biol. 11:586-592; Shi, M. M. et al. 1994. J. Biol. Chem. 269:26512-26517]. The present study demonstrated that the quinone-induced increases in these two enzymes were differentially regulated. L2 cells were exposed to various concentrations of tertiary-butylhydroquinone (TBHQ) for different periods of times. TBHQ increased the activities and the mRNAs for GGT and the catalytic subunit of GCS; however, the time- and concentration-dependencies differed. With 50 microM TBHQ, GCS activity increased significantly by 6 h whereas the activity of GGT was not increased until later. Under the same conditions, the highest GCS-mRNA level observed was at 6 h whereas the mRNA level of GGT increased after 6 h, reached a higher level at 12 h, and then returned to the control level by 24 h. Differences were also observed in the concentration-dependence of mRNA increases between the GGT and GCS. Actinomycin D (an inhibitor of RNA synthesis) abolished the increase of GCS-mRNA but not the increase in GGT-mRNA, suggesting a difference in regulation by TBHQ between these two genes. Nuclear run-on experiments confirmed that the increase of GCS-mRNA, but not GGT-mRNA was due to increased transcription. The increase in GGT-mRNA probably results from a decreased degradation rate. The differences between these two enzymes demonstrate how cells can use multiple mechanisms for regulating gene expression in response to oxidative stress.

Authors+Show Affiliations

Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles 90033, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

8630269

Citation

Liu, R M., et al. "Differential Enhancement of Gamma-glutamyl Transpeptidase and Gamma-glutamylcysteine Synthetase By Tert-butylhydroquinone in Rat Lung Epithelial L2 Cells." American Journal of Respiratory Cell and Molecular Biology, vol. 14, no. 2, 1996, pp. 186-91.
Liu RM, Hu H, Robison TW, et al. Differential enhancement of gamma-glutamyl transpeptidase and gamma-glutamylcysteine synthetase by tert-butylhydroquinone in rat lung epithelial L2 cells. Am J Respir Cell Mol Biol. 1996;14(2):186-91.
Liu, R. M., Hu, H., Robison, T. W., & Forman, H. J. (1996). Differential enhancement of gamma-glutamyl transpeptidase and gamma-glutamylcysteine synthetase by tert-butylhydroquinone in rat lung epithelial L2 cells. American Journal of Respiratory Cell and Molecular Biology, 14(2), pp. 186-91.
Liu RM, et al. Differential Enhancement of Gamma-glutamyl Transpeptidase and Gamma-glutamylcysteine Synthetase By Tert-butylhydroquinone in Rat Lung Epithelial L2 Cells. Am J Respir Cell Mol Biol. 1996;14(2):186-91. PubMed PMID: 8630269.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential enhancement of gamma-glutamyl transpeptidase and gamma-glutamylcysteine synthetase by tert-butylhydroquinone in rat lung epithelial L2 cells. AU - Liu,R M, AU - Hu,H, AU - Robison,T W, AU - Forman,H J, PY - 1996/2/1/pubmed PY - 1996/2/1/medline PY - 1996/2/1/entrez SP - 186 EP - 91 JF - American journal of respiratory cell and molecular biology JO - Am. J. Respir. Cell Mol. Biol. VL - 14 IS - 2 N2 - Sublethal quinone-mediated oxidative stress stimulates increases in the activities and mRNA levels of gamma-glutamyl transpeptidase (GGT) and gamma-glutamylcysteine synthetase (GCS) in rat lung epithelial L2 cells [Kugelman, A. et al. 1994. Am. J. Respir. Cell Mol. Biol. 11:586-592; Shi, M. M. et al. 1994. J. Biol. Chem. 269:26512-26517]. The present study demonstrated that the quinone-induced increases in these two enzymes were differentially regulated. L2 cells were exposed to various concentrations of tertiary-butylhydroquinone (TBHQ) for different periods of times. TBHQ increased the activities and the mRNAs for GGT and the catalytic subunit of GCS; however, the time- and concentration-dependencies differed. With 50 microM TBHQ, GCS activity increased significantly by 6 h whereas the activity of GGT was not increased until later. Under the same conditions, the highest GCS-mRNA level observed was at 6 h whereas the mRNA level of GGT increased after 6 h, reached a higher level at 12 h, and then returned to the control level by 24 h. Differences were also observed in the concentration-dependence of mRNA increases between the GGT and GCS. Actinomycin D (an inhibitor of RNA synthesis) abolished the increase of GCS-mRNA but not the increase in GGT-mRNA, suggesting a difference in regulation by TBHQ between these two genes. Nuclear run-on experiments confirmed that the increase of GCS-mRNA, but not GGT-mRNA was due to increased transcription. The increase in GGT-mRNA probably results from a decreased degradation rate. The differences between these two enzymes demonstrate how cells can use multiple mechanisms for regulating gene expression in response to oxidative stress. SN - 1044-1549 UR - https://www.unboundmedicine.com/medline/citation/8630269/Differential_enhancement_of_gamma_glutamyl_transpeptidase_and_gamma_glutamylcysteine_synthetase_by_tert_butylhydroquinone_in_rat_lung_epithelial_L2_cells_ L2 - http://www.atsjournals.org/doi/full/10.1165/ajrcmb.14.2.8630269?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -