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

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Abstract

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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Authors and Affiliations

  1. Department of Neurosurgery, The General Hospital of PLA, 28 Fuxing Road, Beijing, 100853, China

    Jun Wang & Bao-Min Li

  2. Department of Pathology, The General Hospital of PLA, Beijing, China

    Lu Sun

  3. Department of Ophthalmology, The 309th Hospital of PLA, Beijing, China

    Yan-Fang Si

Authors
  1. Jun Wang
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  2. Lu Sun
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  3. Yan-Fang Si
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  4. Bao-Min Li
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Corresponding author

Correspondence to Bao-Min Li.

Additional information

Jun Wang and Lu Sun contributed equally to this work.

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Wang, J., Sun, L., Si, YF. et al. Overexpression of actin-depolymerizing factor blocks oxidized low-density lipoprotein-induced mouse brain microvascular endothelial cell barrier dysfunction. Mol Cell Biochem 371, 1–8 (2012). https://doi.org/10.1007/s11010-012-1415-7

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  • DOI: https://doi.org/10.1007/s11010-012-1415-7

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