Arsenite stimulates cyclooxygenase-2 expression through activating IκB kinase and nuclear factor κB in primary and ECV304 endothelial cells

Shu-Huei Tsai, Yu-Chih Liang, Linda Chen, Feng Ming Ho, Ming-Shium Hsieh, J. K. Lin

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69 引文 斯高帕斯(Scopus)

摘要

Epidemiological studies have shown that chronic exposure to arsenic can result in liver injury, peripheral neuropathy, arterio]sclerosis, and an increased incidence of cancer of the lung, skin, bladder, and liver. The overexpression of inducible cyclooxygenase-2 (Cox-2) has been associated with vascular inflammation and cellular proliferation. However, the effect of arsenite on Cox-2 gene expression in endothelial cells was left to be investigated. Western Blot analysis of HUVECs revealed a two-fold induction of Cox-2 protein by arsenite. This induction was associated with a two-fold increase of prostaglandin E2 in the media. Furthermore, the level of Cox-2 mRNA was correspondingly elevated as demonstrated by both Northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. Transfection of an immortalized human endothelium cell line (ECV304) with Cox-2 reporter gene constructs demonstrated that the transcription of Cox-2 gene was enhanced by arsenite. This induction was attenuated by pyrrolidine dithiocarbamate (PDTC), an inhibitor of NFκB. In addition, electrophoretic mobility shift assays indicated that NFκB activity was induced by arsenite. The kinase activity assay also indicated that IκB kinase (IKK) activity was induced by arsenite. These findings indicated that the induction of Cox-2 gene transcription by arsenite was through the stimulation of NFκB activity. Arsenite could induce IKK activity, which leads to the phosphorylation and degradation of IκB in ECV304 cells. Therefore, it appears that IKK signaling pathway is involved in arsenite-mediated Cox-2 expression.
原文英語
頁(從 - 到)750-758
頁數9
期刊Journal of Cellular Biochemistry
84
發行號4
DOIs
出版狀態已發佈 - 2002

ASJC Scopus subject areas

  • 生物化學
  • 細胞生物學

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