氧化应激
血脑屏障
活性氧
化学
谷胱甘肽
内皮干细胞
活力测定
紧密连接
细胞生物学
过氧化氢酶
神经毒性
抗氧化剂
药理学
生物化学
细胞
体外
生物
毒性
内分泌学
酶
中枢神经系统
有机化学
作者
Shakila Tobwala,Hsiu-Jen Wang,Joshua W. Carey,William A. Banks,Nuran Erçal
出处
期刊:Toxics
[MDPI AG]
日期:2014-06-05
卷期号:2 (2): 258-275
被引量:40
标识
DOI:10.3390/toxics2020258
摘要
Oxidative stress, which is the loss of balance between antioxidant defense and oxidant production in the cells, is implicated in the molecular mechanism of heavy metal-induced neurotoxicity. Given the key role of lead (Pb) and cadmium (Cd) in inducing oxidative stress, we investigated their role in disrupting the integrity and function of immortalized human brain microvascular endothelial cells (hCMEC/D3). To study this, hCMEC/D3 cells were exposed to control media or to media containing different concentrations of Pb or Cd. Those exposed to Pb or Cd showed significantly higher oxidative stress than the untreated group, as indicated by cell viability, reactive oxygen species (ROS), glutathione (GSH) levels, and catalase enzyme activity. Pb also induced oxidative stress-related disruption of the hCMEC/D3 cell monolayer, as measured by trans-endothelial electrical resistance (TEER), the dextran permeability assay, and the level of tight junction protein, zona occluden protein (ZO-2). However, no significant disruption in the integrity of the endothelial monolayer was seen with cadmium at the concentrations used. Taken together, these results show that Pb and Cd induce cell death and dysfunction in hCMEC/D3 cells and, in the case of Pb, barrier disruption. This suggests blood brain barrier (BBB) dysfunction as a contributing mechanism in Pb and Cd neurotoxicities.
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