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Increased transcription of the regulatory subunit of gamma-glutamylcysteine synthetase in rat lung epithelial L2 cells exposed to oxidative stress or glutathione depletion.
Arch Biochem Biophys. 1997 Jun 01; 342(1):126-33.AB

Abstract

gamma-Glutamylcysteine synthetase (GCS) is the initial and rate-limiting enzyme in the glutathione (GSH) de novo synthesis pathway. GCS is composed of a heavy (73-kDa) catalytic subunit and a light (30-kDa) regulatory subunit, which maintains the Km for glutamate near physiologic concentrations. Previous studies have shown that the steady-state mRNA level and gene transcription for the catalytic subunit increased in response to the redox-cycling quinone 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) in rat lung epithelial L2 cells (M. M. Shi, et al., 1994, J. Biol. Chem. 269,26512-26517). The ratio of the catalytic to regulatory subunit mRNAs varies among tissues, and the anticancer drug cisplatin appears to induce only the catalytic subunit, suggesting independent gene regulation of the two subunits. Nonetheless, the present study found that the steady-state mRNA level and the transcription rate of the GCS regulatory subunit also increased under DMNQ-induced oxidative stress. Changes in mRNA followed a pattern similar to that for the catalytic subunit. The mRNA levels of the two subunits of GCS also both increased above the baseline levels in cells treated with BSO, an inhibitor of GCS enzymatic activity. These data suggest that, under conditions of oxidative stress or glutathione depletion, the regulatory subunit is upregulated at the level of mRNA transcription. Along with the elevation of the catalytic subunit, this increase in GCS regulatory subunit transcription contributes to increases in GCS enzymatic activity and cellular GSH content.

Authors+Show Affiliations

Department of Pathology, School of Medicine, University of Southern California, Los Angeles 90033, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9185621

Citation

Tian, L, et al. "Increased Transcription of the Regulatory Subunit of Gamma-glutamylcysteine Synthetase in Rat Lung Epithelial L2 Cells Exposed to Oxidative Stress or Glutathione Depletion." Archives of Biochemistry and Biophysics, vol. 342, no. 1, 1997, pp. 126-33.
Tian L, Shi MM, Forman HJ. Increased transcription of the regulatory subunit of gamma-glutamylcysteine synthetase in rat lung epithelial L2 cells exposed to oxidative stress or glutathione depletion. Arch Biochem Biophys. 1997;342(1):126-33.
Tian, L., Shi, M. M., & Forman, H. J. (1997). Increased transcription of the regulatory subunit of gamma-glutamylcysteine synthetase in rat lung epithelial L2 cells exposed to oxidative stress or glutathione depletion. Archives of Biochemistry and Biophysics, 342(1), 126-33.
Tian L, Shi MM, Forman HJ. Increased Transcription of the Regulatory Subunit of Gamma-glutamylcysteine Synthetase in Rat Lung Epithelial L2 Cells Exposed to Oxidative Stress or Glutathione Depletion. Arch Biochem Biophys. 1997 Jun 1;342(1):126-33. PubMed PMID: 9185621.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased transcription of the regulatory subunit of gamma-glutamylcysteine synthetase in rat lung epithelial L2 cells exposed to oxidative stress or glutathione depletion. AU - Tian,L, AU - Shi,M M, AU - Forman,H J, PY - 1997/6/1/pubmed PY - 1997/6/1/medline PY - 1997/6/1/entrez SP - 126 EP - 33 JF - Archives of biochemistry and biophysics JO - Arch. Biochem. Biophys. VL - 342 IS - 1 N2 - gamma-Glutamylcysteine synthetase (GCS) is the initial and rate-limiting enzyme in the glutathione (GSH) de novo synthesis pathway. GCS is composed of a heavy (73-kDa) catalytic subunit and a light (30-kDa) regulatory subunit, which maintains the Km for glutamate near physiologic concentrations. Previous studies have shown that the steady-state mRNA level and gene transcription for the catalytic subunit increased in response to the redox-cycling quinone 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) in rat lung epithelial L2 cells (M. M. Shi, et al., 1994, J. Biol. Chem. 269,26512-26517). The ratio of the catalytic to regulatory subunit mRNAs varies among tissues, and the anticancer drug cisplatin appears to induce only the catalytic subunit, suggesting independent gene regulation of the two subunits. Nonetheless, the present study found that the steady-state mRNA level and the transcription rate of the GCS regulatory subunit also increased under DMNQ-induced oxidative stress. Changes in mRNA followed a pattern similar to that for the catalytic subunit. The mRNA levels of the two subunits of GCS also both increased above the baseline levels in cells treated with BSO, an inhibitor of GCS enzymatic activity. These data suggest that, under conditions of oxidative stress or glutathione depletion, the regulatory subunit is upregulated at the level of mRNA transcription. Along with the elevation of the catalytic subunit, this increase in GCS regulatory subunit transcription contributes to increases in GCS enzymatic activity and cellular GSH content. SN - 0003-9861 UR - https://www.unboundmedicine.com/medline/citation/9185621/Increased_transcription_of_the_regulatory_subunit_of_gamma_glutamylcysteine_synthetase_in_rat_lung_epithelial_L2_cells_exposed_to_oxidative_stress_or_glutathione_depletion_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003-9861(97)99997-5 DB - PRIME DP - Unbound Medicine ER -