國家衛生研究院 NHRI:Item 3990099045/2493

NHRI > National Institute of Environmental Health Sciences > Louis W. Chang(1999-2009) > Periodical Articles > Item 3990099045/2493

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Title:	The protective role of intracellular GSH status in the arsenite-induced vascular endothelial dysfunction
Authors:	Tsou, TC;Yeh, SC;Tsai, FY;Chang, LW
Contributors:	Division of Environmental Health and Occupational Medicine
Abstract:	In this study, we used porcine aortic endothelial cells (PAECs) as an in vitro system to investigate the role of intracellular GSH status in arsenite-induced vascular endothelial damage. Exposure of PAECs to L-buthionine sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase (gamma-GCS), markedly enhanced the arsenite-induced cytotoxicity. The data implied that intracellular GSH might play an important role in protection of PAECs from arsenite-induced cytotoxicity. Low concentrations of arsenite exposure increased intracellular GSH concentrations, whereas high concentrations of arsenite exposure decreased intracellular GSH concentrations. We further modulated intracellular GSH concentration by using GSH modulators. N-Acetyl cysteine (NAC) and L-cystine (oxidized L-cysteine), by up-regulating intracellular GSH concentrations, were shown to protect PAECs from arsenite-induced cytotoxicity. On the other hand, BSO and monosodium glutamate (MSG), which down-regulated the intracellular GSH concentrations, further potentiated arsenite-induced cytotoxicity. Moreover, exposure of PAECs to NAC alleviated the arsenite-induced JNK/AP-1 activation and apoptosis, whereas exposure of PAECs to BSO enhanced the arsenite-induced JNK/AP-1 activation and apoptosis. These results indicated that an increase in GSH content represented one of the detoxification mechanisms responding to arsenite exposure and probably played critical roles in the regulation of stress-response signaling molecules as well as in protection of PAECs from arsenite attack.
Keywords:	Chemistry, Medicinal;Chemistry, Multidisciplinary;Toxicology
Date:	2004-02
Relation:	Chemical Research in Toxicology. 2004 Feb;17(2):208-217.
Link to:	http://dx.doi.org/10.1021/tx034202v
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0893-228X&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000189087700010
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=1342331931
Appears in Collections:	[Louis W. Chang(1999-2009)] Periodical Articles [Tsui-Chun Tsou] Periodical Articles

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