Cadmium exposure down-regulates 8-oxoguanine DNA glycosylase expression in rat lung and alveolar epithelial cells

Potts, Ryan; Watkin, R D; Hart, Beth A.

doi:10.1016/s0300-483x(02)00579-6

Cited by 46 publications

(26 citation statements)

References 28 publications

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“…Here we show that the oxidative stress induced by a short exposure of human cells to a toxic concentration of cadmium results in nearly complete but reversible inactivation of the 8-oxoG DNA glycosylase activity of hOGG1. Chronic exposure to low doses of cadmium lowers the cellular activity of OGG1 in animal models (36,37) or in human cells (47). In the former cases, the cadmium-induced reduction of OGG1 activity was paralleled by lower enzyme levels most likely resulting from inhibition of gene expression at the transcriptional level.…”

Section: Discussionmentioning

confidence: 99%

“…Not only could the oxidative stress generated by cadmium exposure yield oxidative DNA damage, but the heavy metal was also described as being an inhibitor of oxidative DNA repair pathways (11). In particular, exposure to cadmium was shown to reduce the 8-oxoG DNA glycosylase activity levels from extracts of both lung tissue from rats and rat lung cell lines (36,37). These effects were associated with lower levels of protein expression.…”

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confidence: 99%

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Redox Regulation of Human OGG1 Activity in Response to Cellular Oxidative Stress

Bravard

Vacher

Gouget

et al. 2006

Molecular and Cellular Biology

143

108

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8-Oxoguanine (8-oxoG), a common and mutagenic form of oxidized guanine in DNA, is eliminated mainly through base excision repair. In human cells its repair is initiated by human OGG1 (hOGG1), an 8-oxoG DNA glycosylase. We investigated the effects of an acute cadmium exposure of human lymphoblastoid cells on the activity of hOGG1. We show that coinciding with alteration of the redox cellular status, the 8-oxoG DNA glycosylase activity of hOGG1 was nearly completely inhibited. However, the hOGG1 activity returned to normal levels once the redox cellular status was normalized. In vitro, the activity of purified hOGG1 was abolished by cadmium and could not be recovered by EDTA. In cells, however, the reversible inactivation of OGG1 activity by cadmium was strictly associated with reversible oxidation of the protein. Moreover, the 8-oxoG DNA glycosylase activity of purified OGG1 and that from crude extracts were modulated by cysteine-modifying agents. Oxidation of OGG1 by the thiol oxidant diamide led to inhibition of the activity and a protein migration pattern similar to that seen in cadmiumtreated cells. These results suggest that cadmium inhibits hOGG1 activity mainly by indirect oxidation of critical cysteine residues and that excretion of the metal from the cells leads to normalization of the redox cell status and restoration of an active hOGG1. The results presented here unveil a novel redox-dependent mechanism for the regulation of OGG1 activity.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Redox Regulation of Human OGG1 Activity in Response to Cellular Oxidative Stress

Bravard

Vacher

Gouget

et al. 2006

Molecular and Cellular Biology

143

108

View full text Add to dashboard Cite

show abstract

“…Effect of Cadmium on hOGG1 Expression-Experiments were conducted to confirm that cadmium suppresses hOGG1 expression in human fibroblasts and cervix cancer cells, as has been documented previously for rodent lung epithelial cells (38). GM00637 and HeLa S3 cells were treated without or with 10 M CdCl 2 , and hOGG1 protein levels were determined in the attached cells after a 24-h CdCl 2 treatment.…”

Section: Resultsmentioning

confidence: 99%

“…Similarly, Potts et al (62) have shown that hydrogen peroxide-induced 8-oxoG accumulation is much higher in cadmium-adapted epithelial cells compared with non-adapted cells. Moreover, Potts et al (38) reported that cadmium is effective as an inhibitor of OGG1 expression both in vivo in rats exposed to aerosols of cadmium acetate and in vitro in a rat lung epithelial cell line. This down-regulation was observed at both the mRNA and protein levels, and it was produced by 10 M cadmium, which caused no loss in the viability of the cell culture.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, Potts et al (38) have clearly shown that cadmium inhibits oxidative DNA repair by the down-regulation of OGG1 in rat lung epithelial cells and that this down-regulation of OGG1 is related to cadmium-mediated decreases in OGG1 mRNA. Therefore, there has been considerable interest in determining whether this phenomenon also occurs in human cells and, if so, which transcription factor mediates the downregulated OGG1 expression in cadmium-treated cells.…”

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confidence: 99%

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Cadmium Down-regulates Human OGG1 through Suppression of Sp1 Activity

Youn

Kim

Lee

et al. 2005

Journal of Biological Chemistry

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Cadmium is a well known human and animal carcinogen and is a ubiquitous contaminant in the environment. Although the carcinogenic mechanism of cadmium is a multifactorial process, oxidative DNA damage is believed to be of prime importance. In particular, cadmium suppresses the capacity of cells to repair oxidative DNA damage. In this study, cadmium treatment led to a significant increase in ␥-ray-induced 8-oxoguanine (8-oxoG) formation. Western blotting and semiquantitative reverse transcription-PCR revealed that cadmium treatment caused a decrease in the expression level of human OGG1 (8-oxoguanine-DNA glycosylase-1; hOGG1) in human fibroblast GM00637 and HeLa S3 cells. In addition, the cadmium-mediated decrease in hOGG1 transcription was the result of decreased binding of the transcription factor Sp1 to the hOGG1 promoter. Finally, we show that an increase in the functional hOGG1 expression level could inhibit the cadmium-mediated increase in ␥-ray-induced 8-oxoG accumulation as well as in ␥-radiation-induced mutation frequency at the HPRT (hypoxanthine-guanine phosphoribosyltransferase) gene locus. These results suggest that cadmium attenuates removal of ␥-ray-induced 8-oxoG adducts, which in turn increases the mutation frequency, and that this effect might, at least in part, result from suppression of hOGG1 transcription via inactivation of Sp1 as a result of cadmium treatment.

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Cadmium und seine anorganischen Verbindungen [MAK Value Documentation in German language, 2004]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 39. Lieferung, Ausgabe 2004 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Wirkungsmechanismus Toxikokinetik und Metabolismus Aufnahme, Verteilung, Ausscheidung Metabolismus Erfahrungen beim Menschen Einmalige Exposition Wiederholte Exposition Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Tierexperimentelle Befunde und In‐vitro‐Untersuchungen Akute Toxizität Subakute, subchronische und chronische Toxizität Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogene Wirkung Bewertung

show abstract

Cadmium exposure down-regulates 8-oxoguanine DNA glycosylase expression in rat lung and alveolar epithelial cells

Cited by 46 publications

References 28 publications

Redox Regulation of Human OGG1 Activity in Response to Cellular Oxidative Stress

Redox Regulation of Human OGG1 Activity in Response to Cellular Oxidative Stress

Cadmium Down-regulates Human OGG1 through Suppression of Sp1 Activity

Cadmium und seine anorganischen Verbindungen [MAK Value Documentation in German language, 2004]

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