Cadmium resistance in A549 cells correlates with elevated glutathione content but not antioxidant enzymatic activities

Hatcher, Emiko L.; Chen, Yan; Kang, Y. James

doi:10.1016/0891-5849(95)00099-j

Cited by 85 publications

(43 citation statements)

References 34 publications

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“…The present result was consistent with the previous finding (Hu et al 2005). There are three possible hypotheses that can explain the increase of GSH in cells (Hatcher et al 1995): (a) enhanced activity of GR (reduce GSSG to GSH); (b) extracellular degradation of GSH by c-glutamyltranspeptidase (c-GT) enzyme and elevation of the substrate concentrations for intracellular GSH new synthesis; and (c) enhanced expression of c-glutamylcysteine synthetase (c-GCS) enzyme causing enhanced cellular GSH synthesis. GR activities in treated cells were activated (Table 2).…”

Section: Resultssupporting

confidence: 83%

The Role of Glutathione Metabolism in Tolerance of Tobacco BY-2 Suspension Cells to Microcystin-RR

Huang

Xing

et al. 2008

Bull Environ Contam Toxicol

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This study was undertaken to investigate the role of the glutathione-involved detoxifying mechanism in defending the tobacco BY-2 suspension cells against microcystin-RR (MC-RR). Analysis showed that exposure of the cells to different concentrations of MC-RR (0.1, 1 and 10 lg/mL) for 0-6 days resulted in a time and concentration-dependent decrease in cell viability and increase in reactive oxygen species (ROS) content. Reduced glutathione (GSH) and total glutathione (tGSH) content as well as glutathione reductase (GR), glutathione peroxidase (GPX) and glutathione-S-transferase (GST) activities significantly increased after 3-4 days exposure in the highest two concentration treated groups, while decreased until reaching the control values except for GPX at day 6. Oxidized glutathione (GSSG) content markedly increased compared with control in high concentration MC-RR treated group after 6 days exposure. The GSH/GSSG ratio was much higher than control in 10 lg/mL MC-RR treated group at day 4, but after 6 days exposure, the ratios in all treated groups were lower than that of the control group.

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Section: Resultssupporting

confidence: 83%

The Role of Glutathione Metabolism in Tolerance of Tobacco BY-2 Suspension Cells to Microcystin-RR

Huang

Xing

et al. 2008

Bull Environ Contam Toxicol

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“…This is followed by a sustained increase in GSH at 12-24 h in lungs in vivo, and in human alveolar and bronchial epithelial and endothelial cells in vitro, which is associated with an increased expression of mRNA for the GCL subunit genes for GSH synthesis [35][36][37]. However, in the present study, the authors found a significant decrease of GCLM mRNA expression in the BAL cells of smoking subjects compared with never-smokers.…”

Section: Discussioncontrasting

confidence: 56%

Glutamate-cysteine ligase modulatory subunit in BAL alveolar macrophages of healthy smokers

Neurohr

Lenz²,

Ding³

et al. 2003

Eur Respir J

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The antioxidant glutathione (GSH) is increased in the epithelial lining fluid (ELF) of chronic smokers. The rate-limiting enzyme in GSH synthesis is glutamate-cysteine ligase (GCL), also known as c-glutamylcysteine synthetase, consisting of a heavy, catalytic (GCLC) and a light, modulatory (GCLM) subunit.To determine the contribution of bronchoalveolar lavage (BAL) cells to GSH levels in ELF, BAL was performed in eight smokers and eight never-smokers. Intra-and extracellular total glutathione (GSHt) levels and GCL subunit expression were assessed.GSHt was increased in ELF from smokers (1,090.1¡163.0 mM versus 559.2¡ 48.2 mM). GSHt content of BAL cells (nmol?mg protein -1 ) was decreased in smokers without differences reaching statistical significance (8.0¡1.4 versus 12.4¡2.6). GCLM expression was also reduced in smokers (0.6¡0.1 versus 2.8¡0.4) and correlated with intracellular GSHt content. There was no significant difference in GCLC expression and in differential cell counts in BAL fluid.The authors conclude that smoking does increase glutathione levels in the epithelial lining fluid but not intracellular levels in bronchoalveolar lavage cells. The data suggest that the intracellular glutathione concentration of bronchoalveolar lavage cells (predominately alveolar macrophages) is regulated by the modulatory glutamatecysteine ligase subunit rather than the catalytic subunit. Eur Respir J 2003; 22: 82-87.

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“…~K3CS-HS has been shown to be induced by various redoxregulating agents [24][25][26][27] but the precise stimulus for the induction of ~(3CS-HS mRNA following CSC exposure is not clear. Aqueous solution of CSC contains highly electrophilic compounds capable of generating H202 [28] and heavy metals, such as cadmium [10], which may modulate the AP-1 transcription factor [29,30].…”

Section: Resultsmentioning

confidence: 99%

Induction of γ‐glutamylcysteine synthetase by cigarette smoke is associated with AP‐1 in human alveolar epithelial cells

Rahman¹,

Smith

Lawson³

et al. 1996

FEBS Letters

152

117

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Increased levels of glutathione (GSH) occur in the epithelial lining fluid (ELF) of chronic cigarette smokers. Therefore we investigated the effect of cigarette smoke condensate solution (CSC) on GSH synthesis and the regulation of T-glutamylcysteine synthetase (~CS) in human type II alveolar epithelial cells (A549). CSC exposure increased GSH levels, TGCS activity and ~CS heavy subunit (HS) mRNA, as well as increasing DNA binding of the activator protein-1 (AP-1) and the human antioxidant response element (hARE). Transfection of deletion constructs of the ~GCS-HS promoter in a chloramphenicol acetyl transferase (CAT) reporter system revealed that an hARE, present within promoter, is not required tot the CSC mediated induction. We conclude that CSC induction of ~GCS-HS expression is associated with AP-1/AP-I-like responsive elements.

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Cadmium resistance in A549 cells correlates with elevated glutathione content but not antioxidant enzymatic activities

Cited by 85 publications

References 34 publications

The Role of Glutathione Metabolism in Tolerance of Tobacco BY-2 Suspension Cells to Microcystin-RR

The Role of Glutathione Metabolism in Tolerance of Tobacco BY-2 Suspension Cells to Microcystin-RR

Glutamate-cysteine ligase modulatory subunit in BAL alveolar macrophages of healthy smokers

Induction of γ‐glutamylcysteine synthetase by cigarette smoke is associated with AP‐1 in human alveolar epithelial cells

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