國家衛生研究院 NHRI:Item 3990099045/1287

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Title:	Inhibition of cadmium-induced oxidative injury in rat primary astrocytes by the addition of antioxidants and the reduction of intracellular calcium
Authors:	Yang, CS;Tzou, BC;Liu, YP;Tsai, MJ;Shyue, SK;Tzeng, SF
Contributors:	Center for Nanomedicine Research
Abstract:	Exposure of the brain to cadmium ions (Cd2+) is believed to lead to neurological disorders of the central nervous system (CNS). In this study, we tested the hypothesis that astrocytes, the major CNS-supporting cells, are resistant to Cd2+ induced injury compared with cortical neurons and microglia (CNS macrophages). However, treatment with CdCl2 for 24 h at concentrations higher than 20 mu M substantially induced astrocytic cytotoxicity, which also resulted from long-term exposure to 5 mu M of CdCl2. Intracellular calcium levels were found to rapidly increase after the addition of CdCl2 into astrocytes, which led to a rise in reactive oxygen species (ROS) and to mitochondrial impairment. In accordance, preexposure to the extracellular calcium chelator EGTA effectively reduced ROS production and increased survival of Cd2+-treated astrocytes. Adenovirus-mediated transfer of superoxide dismutase (SOD) or glutathione peroxidase (GPx) genes increased survival of Cd2+-exposed astrocytes. In addition, increased ROS generation and astrocytic cell death due to Cd2+ exposure was inhibited when astrocytes were treated with the polyphenolic compound ellagic acid (EA). Taken together, Cd2+ induced astrocytic cell death resulted from disrupted calcium homeostasis and an increase in ROS. Moreover, our findings demonstrate that enhancement of the activity of intracellular antioxidant enzymes and supplementation with a phenolic compound, a natural antioxidant, improves survival of Cd2+-primed astrocytes. This information provides a useful approach for treating Cd2+ induced CNS neurological disorders.
Keywords:	Biochemistry & Molecular Biology;Cell Biology
Date:	2008-02-15
Relation:	Journal of Cellular Biochemistry. 2008 Feb;103(3):825-834.
Link to:	http://dx.doi.org/10.1002/jcb.21452
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0730-2312&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000253132800012
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=39049149164
Appears in Collections:	[Chung-Shi Yang] Periodical Articles

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