國家衛生研究院 NHRI:Item 3990099045/2469
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    题名: Arsenite induces endothelial cytotoxicity by down-regulation of vascular endothelial nitric oxide synthase
    作者: Tsou, TC;Tsai, FY;Hsieh, YW;Li, LA;Yeh, SC;Chang, LW
    贡献者: Division of Environmental Health and Occupational Medicine
    摘要: Epidemiological studies have demonstrated a high association of inorganic arsenic exposure with vascular diseases. Recent research has also linked this vascular damage to impairment of endothelial nitric oxide synthase (eNOS) function by arsenic exposure. However, the role of eNOS in regulating the arsenite-induced vascular dysfunction still remains to be clarified. In our present study, we investigated the effect of arsenite on Aktl and eNOS and its involvement in cytotoxicity of vascular endothelial cells. Our study demonstrated that arsenite decreased the protein levels of both Aktl and eNOS accompanied with increased levels of ubiquitination of total cell lysates. We found that inhibition of the ubiquitin-proteasome pathway by MG-132 could partially protect Aktl and eNOS from degradation by arsenite together with a proportional protection from the arsenite-induced cytoxicity. Moreover, up-regulation of eNOS protein expression significantly attenuated the arsenite-induced cytotoxicity and eNOS activity could be significantly inhibited after incubation with arsenite for 24 h in a cell-free system. Our study indicated that endothelial eNOS activity could be attenuated by arsenite via the ubiquitin-proteasome-mediated degradation of Aktl/eNOS as well as via direct inhibition of eNOS activity. Our study also demonstrated that eNOS actually played a protective role in arsenite-induced cytoxicity. These observations supported the hypothesis that the impairment of eNOS function by arsenite is one of the mechanisms leading to vascular changes and diseases. (c) 2005 Elsevier Inc. All rights reserved.
    关键词: Pharmacology & Pharmacy;Toxicology
    日期: 2005-11-01
    關聯: Toxicology and Applied Pharmacology. 2005 Nov;208(3):277-284.
    Link to: http://dx.doi.org/10.1016/j.taap.2005.03.001
    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:000233057400008
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=26844444806
    显示于类别:[張惠華(1999-2009)] 期刊論文
    [李立安] 期刊論文
    [鄒粹軍] 期刊論文

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