國家衛生研究院 NHRI:Item 3990099045/4463
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    题名: Arsenite enhances tumor necrosis factor-alpha-induced expression of vascular cell adhesion molecule-1
    其它题名: Arsenite enhances tumor necrosis factor-α-induced expression of vascular cell adhesion molecule-1
    作者: Tsou, TC;Yeh, SC;Tsai, EM;Tsai, FY;Chao, HR;Chang, LW
    贡献者: Division of Environmental Health and Occupational Medicine
    摘要: Epidemiological studies demonstrated a high association of vascular diseases with arsenite exposure. We hypothesize that arsenite potentiates the effect of proinflammatory cytokines on vascular endothelial cells, and hence contributes to atherosclerosis. In this study, we investigated the effect of arsenite and its induction of glutathione (GSH) on vascular cell adhesion molecule-1 (VCAM-1) protein expression in human umbilical vein endothelial cells (HLTVECs) in response to tumor necrosis factor-alpha (TNF-alpha), a typical proinflammatory cytokine. Our study demonstrated that arsenite pretreatment potentiated the TNF-alpha-induced VCAM-1 expression with up-regulations of both activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappa B). To elucidate the role of GSH in regulation of AP-1, NF-kappa B, and VCAM-1 expression, we employed L-buthionine (S,R)-sulfoximine (BSO), a specific gamma-glutamyleysteine synthetase (gamma-GCS) inhibitor, to block intracellular GSH synthesis. Our investigation revealed that, by depleting GSH, arsenite attenuated the TNF-alpha-induced VCAM-1 expression as well as a potentiation of AP-1 and an attenuation of NF-kappa B activations by TNF-alpha. Moreover, we found that depletion of GSH would also attenuate the TNF-alpha-induced VCAM-1 expression with a down-regulation of the TNF-alpha-induced NF-kappa B activation and without significant effect on AP-1. On the other hand, the TNF-alpha-induced VCAM-1 expression could be completely abolished by inhibition of AP-1 or NF-kappa B activity, suggesting that activation of both AP-1 and NF-kappa B was necessary for VCAM-1 expression. In summary, we demonstrate that arsenite enhances the TNF-alpha-induced VCAM-1 expression in HUVECs via regulation of AP-1 and NF-kappa B activities in a GSH-sensitive manner. Our present study suggested a potential mechanism for arsenite in the induction of vascular inflammation and vascular diseases via modulating the actions of proinflammatory cytokines.
    日期: 2005-11
    關聯: Toxicology and Applied Pharmacology. 2005 Nov;209(1):10-18.
    Link to: http://dx.doi.org/10.1016/j.taap.2005.03.006
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0041-008X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000233378100002
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=27544485712
    显示于类别:[張惠華(1999-2009)] 期刊論文
    [鄒粹軍] 期刊論文

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