Overexpression of actin-depolymerizing factor blocks oxidized low-density lipoprotein-induced mouse brain microvascular endothelial cell barrier dysfunction

被引：18
作者：
Wang, Jun [1 ]
Sun, Lu [2 ]
Si, Yan-Fang [3 ]
Li, Bao-Min [1 ]
机构：
[1] Gen Hosp PLA, Dept Neurosurg, Beijing 100853, Peoples R China
[2] Gen Hosp PLA, Dept Pathol, Beijing 100853, Peoples R China
[3] 309th Hosp PLA, Dept Ophthalmol, Beijing, Peoples R China
来源：
MOLECULAR AND CELLULAR BIOCHEMISTRY | 2012年 / 371卷 / 1-2期
关键词：
Actin-depolymerizing factor; Endothelial; Blood-brain barrier; Reactive oxygen species; Actin cytoskeleton; APOPTOTIC CELLS; IN-VIVO; PERMEABILITY; LDL; EXPRESSION; INCREASES; PHAGOCYTOSIS; INHIBITION; COFILIN-1; PROTEINS;
D O I：
10.1007/s11010-012-1415-7
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
The aim of present work was to elucidate the role of actin-depolymerizing factor (ADF), an important regulator of actin cytoskeleton, in the oxidized low-density lipoprotein (ox-LDL)-induced blood-brain barrier (BBB) disruption. The primary mouse brain microvascular endothelial cells (MBMECs) were exposed to ox-LDL. Treatment with LDL served as control. It was found that ADF mRNA level and protein expression were decreased when exposed to ox-LDL in MBMECs. Then, we investigated the influence of ADF overexpression on ox-LDL-treated MBMECs. Structurally, overexpression of ADF inhibited ox-LDL-induced F-actin formation. Functionally, overexpression of ADF attenuated ox-LDL-induced disruption of endothelial barrier marked by restoration of transendothelial electrical resistance, permeability of Evans Blue and expression of tight junction-associated proteins including ZO-1 and occludin, and blocked ox-LDL-induced oxidative stress marked by inhibition of reactive oxygen species (ROS) formation and activity of NADPH oxidase and Nox2 expression. However, overexpression of ADF in control cells had no significant effect on endothelial permeability and ROS formation. In conclusion, overexpression of ADF blocks ox-LDL-induced disruption of endothelial barrier. In addition, siRNA-mediated downregulation of ADF expression aggravated ox-LDL-induced disruption of endothelial barrier and ROS formation. These findings identify ADF as a key signaling molecule in the regulation of BBB integrity and suggest that ADF might be used as a target to modulate diseases accompanied by ox-LDL-induced BBB compromise.
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页码：1 / 8
页数：8
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