Overexpression of actin-depolymerizing factor blocks oxidized low-density lipoprotein-induced mouse brain...

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Oxidized low-density lipoprotein (ox-LDL) is implicated in blood-brain barrier (BBB) disruption.
• The role of actin-depolymerizing factor (ADF) in ox-LDL-induced BBB compromise is not fully understood.

Purpose of the Study:

• To investigate the role of ADF in ox-LDL-induced BBB disruption.
• To explore ADF as a potential therapeutic target for BBB integrity.

Main Methods:

• Primary mouse brain microvascular endothelial cells (MBMECs) were treated with ox-LDL.
• ADF expression was modulated using overexpression and siRNA-mediated downregulation.
• BBB integrity was assessed by measuring transendothelial electrical resistance, Evans Blue permeability, and tight junction protein expression (ZO-1, occludin).
• Oxidative stress markers, including reactive oxygen species (ROS) formation, NADPH oxidase activity, and Nox2 expression, were evaluated.

Main Results:

• Ox-LDL exposure decreased ADF mRNA and protein levels in MBMECs.
• ADF overexpression inhibited ox-LDL-induced F-actin formation and attenuated BBB disruption.
• ADF overexpression restored endothelial barrier function and reduced ROS formation.
• Downregulation of ADF aggravated ox-LDL-induced BBB disruption and ROS production.

Conclusions:

• ADF plays a protective role against ox-LDL-induced BBB disruption.
• ADF overexpression effectively mitigates BBB damage and oxidative stress.
• ADF is a key regulator of BBB integrity and a potential therapeutic target for diseases involving BBB compromise.