Inhibition of cadmium-induced oxidative injury in rat primary astrocytes by the addition of antioxidants and the reduction of intracellular calcium

Chung Shi Yang, Bo Cheng Tzou, Yu Peng Liu, May Jywan Tsai, Song Kun Shyue, Shun Fen Tzeng

研究成果: Article同行評審

64 引文 斯高帕斯(Scopus)

摘要

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 μM substantially induced astrocytic cytotoxicity, which also resulted from long-term exposure to 5 μM 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 Cd 2+ exposure was inhibited when astrocytes were treated with the polyphenols 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 Cd 2+-primed astrocytes. This information provides a useful approach for treating Cd2+-induced CNS neurological disorders.

原文English
頁(從 - 到)825-834
頁數10
期刊Journal of Cellular Biochemistry
103
發行號3
DOIs
出版狀態Published - 2008 2月 15

All Science Journal Classification (ASJC) codes

  • 生物化學
  • 分子生物學
  • 細胞生物學

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