Tags

Type your tag names separated by a space and hit enter

Cadmium-induced elevations in the gene expression of the regulatory subunit of gamma-glutamylcysteine synthetase in rat lung and alveolar epithelial cells.
Toxicology. 2000 Oct 26; 151(1-3):45-54.T

Abstract

The controlled step in de novo glutathione (GSH) synthesis is catalyzed by gamma-glutamylcysteine synthetase (gamma-GCS), a dimeric enzyme consisting of a heavy catalytic subunit (gamma-GCS-HS) and a light regulatory subunit (gamma-GCS-LS). We have previously reported that exposure to cadmium (Cd) induces pulmonary gamma-GCS-HS mRNA and protein, and that these alterations are accompanied by increases in GSH synthesis and its steady-state level. The current study was designed to test the hypothesis that Cd exposure also up-regulates the expression of the regulatory gamma-GCS subunit. By using northern blotting, we have demonstrated that a single Cd aerosol exposure of adult male Lewis rats results in time- and dose-dependent increases in pulmonary levels of gamma-GCS-LS mRNA. Transcripts of gamma-GCS-LS in rat lung are maximally elevated (8-fold) 2 h following Cd inhalation exposure and remain significantly higher than air controls at 24 h. This response is highly correlated with Cd dose, ranging from 0.9 to 5 mg Cd per m(3), and with lung Cd burden. We also observed Cd-induced up-regulation of gamma-GCS-LS mRNA expression in alveolar epithelial cells exposed to Cd in vitro, either acutely or after repeated passaging in Cd-containing medium. The magnitude of the gamma-GCS regulatory subunit induction observed in Cd-treated cells was approximately five times greater than the induction of the catalytic subunit. These modifications in the expression of gamma-GCS subunits may offer protection from Cd toxicity.

Authors+Show Affiliations

Biochemistry Department, College of Medicine, University of Vermont, Room C-440, Given Medical Building, 05405-0068, Burlington, VT, 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

11074299

Citation

Shukla, G S., et al. "Cadmium-induced Elevations in the Gene Expression of the Regulatory Subunit of Gamma-glutamylcysteine Synthetase in Rat Lung and Alveolar Epithelial Cells." Toxicology, vol. 151, no. 1-3, 2000, pp. 45-54.
Shukla GS, Chiu J, Hart BA. Cadmium-induced elevations in the gene expression of the regulatory subunit of gamma-glutamylcysteine synthetase in rat lung and alveolar epithelial cells. Toxicology. 2000;151(1-3):45-54.
Shukla, G. S., Chiu, J., & Hart, B. A. (2000). Cadmium-induced elevations in the gene expression of the regulatory subunit of gamma-glutamylcysteine synthetase in rat lung and alveolar epithelial cells. Toxicology, 151(1-3), 45-54.
Shukla GS, Chiu J, Hart BA. Cadmium-induced Elevations in the Gene Expression of the Regulatory Subunit of Gamma-glutamylcysteine Synthetase in Rat Lung and Alveolar Epithelial Cells. Toxicology. 2000 Oct 26;151(1-3):45-54. PubMed PMID: 11074299.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cadmium-induced elevations in the gene expression of the regulatory subunit of gamma-glutamylcysteine synthetase in rat lung and alveolar epithelial cells. AU - Shukla,G S, AU - Chiu,J, AU - Hart,B A, PY - 2000/11/14/pubmed PY - 2001/2/28/medline PY - 2000/11/14/entrez SP - 45 EP - 54 JF - Toxicology JO - Toxicology VL - 151 IS - 1-3 N2 - The controlled step in de novo glutathione (GSH) synthesis is catalyzed by gamma-glutamylcysteine synthetase (gamma-GCS), a dimeric enzyme consisting of a heavy catalytic subunit (gamma-GCS-HS) and a light regulatory subunit (gamma-GCS-LS). We have previously reported that exposure to cadmium (Cd) induces pulmonary gamma-GCS-HS mRNA and protein, and that these alterations are accompanied by increases in GSH synthesis and its steady-state level. The current study was designed to test the hypothesis that Cd exposure also up-regulates the expression of the regulatory gamma-GCS subunit. By using northern blotting, we have demonstrated that a single Cd aerosol exposure of adult male Lewis rats results in time- and dose-dependent increases in pulmonary levels of gamma-GCS-LS mRNA. Transcripts of gamma-GCS-LS in rat lung are maximally elevated (8-fold) 2 h following Cd inhalation exposure and remain significantly higher than air controls at 24 h. This response is highly correlated with Cd dose, ranging from 0.9 to 5 mg Cd per m(3), and with lung Cd burden. We also observed Cd-induced up-regulation of gamma-GCS-LS mRNA expression in alveolar epithelial cells exposed to Cd in vitro, either acutely or after repeated passaging in Cd-containing medium. The magnitude of the gamma-GCS regulatory subunit induction observed in Cd-treated cells was approximately five times greater than the induction of the catalytic subunit. These modifications in the expression of gamma-GCS subunits may offer protection from Cd toxicity. SN - 0300-483X UR - https://www.unboundmedicine.com/medline/citation/11074299/Cadmium_induced_elevations_in_the_gene_expression_of_the_regulatory_subunit_of_gamma_glutamylcysteine_synthetase_in_rat_lung_and_alveolar_epithelial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300483X00002638 DB - PRIME DP - Unbound Medicine ER -