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Upregulation of glutathione-related genes and enzyme activities in cultured human cells by sublethgal concentrations of inorganic arsenic

Schuliga, Michael, Chouchane, Salem and Snow, Elizabeth T. 2002, Upregulation of glutathione-related genes and enzyme activities in cultured human cells by sublethgal concentrations of inorganic arsenic, Toxicological sciences, vol. 70, no. 2, pp. 183-192, doi: 10.1093/toxsci/70.2.183.

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Title Upregulation of glutathione-related genes and enzyme activities in cultured human cells by sublethgal concentrations of inorganic arsenic
Author(s) Schuliga, Michael
Chouchane, Salem
Snow, Elizabeth T.
Journal name Toxicological sciences
Volume number 70
Issue number 2
Start page 183
End page 192
Publisher Oxford University Press
Place of publication Oxford, England
Publication date 2002-12
ISSN 1096-6080
Keyword(s) arsenite
glutathione
glutathione reductase
keratinocytes
gene expression
Summary Inorganic arsenic (jAs), a known human carcinogen, acts as a tumor promoter in part by inducing a rapid burst of reactive oxygen species (ROS) in mammalian cells. This causes oxidative stress and a subsequent increase in the level of cellular glutathione (GSH). Glutathione, a ubiquitous reducing sulfhydryl tripeptide, is involved in ROS detoxification and its increase may be part of an adaptive response to the oxidative stress. Glutathione related enzymes including glutathione reductase (GR) and glutathione S-transferase (GST) also play key roles in these processes. In this study the regulatory effects of inorganic arsenite (As111) on the activities of GSH-related enzymes were investigated in cultured human keratinocytes. Substantial increases in GR enzyme activity and mRNA levels were shown in keratinocytes and other human cell lines after exposure to low, subtoxic, micromolar concentrations of As111 for 24 h. Upregulation of GSH synthesis paralleled the upregulation of GR as shown by increases in glutamatecysteine lyase (GeL) enzyme activity and mRNA levels, cystine uptake, and intracellular GSH levels. Glutathione S-transferase activity was also shown to increase slightly in keratinocytes, but not in fibroblasts or breast tumor cells. Overall the results show that sublethal arsenic induces a multicomponent response in human keratinocytes that involves upregulation of parts, but not all of the GSH system and counteracts the acute toxic effects of jAs. The upregulation of GR has not previously been shown to be an integral part of this response, although GR is critical for maintaining levels of reduced GSH.
Language eng
DOI 10.1093/toxsci/70.2.183
Field of Research 060405 Gene Expression (incl Microarray and other genome-wide approaches)
HERDC Research category C1 Refereed article in a scholarly journal
Persistent URL http://hdl.handle.net/10536/DRO/DU:30001725

Document type: Journal Article
Collection: School of Biological and Chemical Sciences
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