Involvement of reactive oxygen species in arsenite-induced downregulation of phospholipid hydroperoxide glutathione peroxidase in human epidermoid carcinoma A431 cells

Huei Sheng Huang, Wen Chang Chang, Ching Jiunn Chen

研究成果: 雜誌貢獻文章

43 引文 斯高帕斯(Scopus)

摘要

Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is unique in the substrate specificity among the glutathione peroxidase family because it can interact with lipophilic substrates, including the peroxidized phospholipids and cholesterol, and reduce these hydroperoxide to hydroxide compounds. However, what kinds of ligand can regulate the PHGPx expression is still unknown. In the present study, we found that sodium arsenite induced downregulation of mRNA, protein expression, and enzyme activity of PHGPx in time- and dose-dependent manners. At the same time, it upregulated mRNA and protein expression of p21WAF1/CIP1. With the aid of agarose gel electrophoresis, and propidium iodide and annexin-V staining, we found that treatment of 30 μM sodium arsenite for 24 h induced apoptosis in human epidermoid carcinoma A431 cells and EA.hy926 cells. An increase of intracellular peroxide levels was measured by flow cytometry using 2′,7′-dichlorofluorescin diacetate (DCFH-DA) after treatment of arsenite. Overexpression of PHGPx prevented arsenite-induced increase of intracellular peroxide levels, downregulation of PHGPx, upregulation of p21WAF1/CIP1, and apoptosis in A431 cells. N-Acetyl-L-cysteine also significantly prevented arsenite-induced effects in A431 cells. Therefore, we concluded that reactive oxygen species were involved in arsenite-induced downregulation of PHGPx, upregulation of p21WAF1/CIP1, and apoptosis in A431 cells.

原文英語
頁(從 - 到)864-873
頁數10
期刊Free Radical Biology and Medicine
33
發行號6
DOIs
出版狀態已發佈 - 九月 15 2002
對外發佈Yes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Medicine(all)
  • Toxicology

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