國家衛生研究院 NHRI:Item 3990099045/2469

NHRI > National Institute of Environmental Health Sciences > Louis W. Chang(1999-2009) > Periodical Articles > Item 3990099045/2469

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/2469

Title:	Arsenite induces endothelial cytotoxicity by down-regulation of vascular endothelial nitric oxide synthase
Authors:	Tsou, TC;Tsai, FY;Hsieh, YW;Li, LA;Yeh, SC;Chang, LW
Contributors:	Division of Environmental Health and Occupational Medicine
Abstract:	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.
Keywords:	Pharmacology & Pharmacy;Toxicology
Date:	2005-11-01
Relation:	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
Appears in Collections:	[Louis W. Chang(1999-2009)] Periodical Articles [Lih-Ann Li] Periodical Articles [Tsui-Chun Tsou] Periodical Articles

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