Resveratrol protects against oxidized LDL-induced breakage of the blood-brain barrier by lessening disruption of tight junctions and apoptotic insults to mouse cerebrovascular endothelial cells.
Cerebrovascular endothelial cells (CEC) comprise the blood-brain barrier (BBB). In a previous study, we showed that oxidized LDL (oxLDL) can induce apoptosis of mouse CEC. Resveratrol possesses chemopreventive potential. This study aimed to evaluate the effects of resveratrol on oxLDL-induced insults to mouse CEC and its possible mechanisms. Exposure of mouse CEC to 200 μmol/L oxLDL for 1 h did not cause cell death but significantly altered the permeability and transendothelial electrical resistance of the cell monolayer. However, resveratrol completely normalized such injury. As for the mechanisms, resveratrol completely protected oxLDL-induced disruption of F-actin and microtubule cytoskeletons as well as occludin and zona occludens-1 (ZO-1) tight junctions. The oxLDL-induced decreases in the mitochondrial membrane potential and intracellular ATP levels were normalized by resveratrol. Exposure of mouse CEC to 200 μmol/L oxLDL for 24 h elevated oxidative stress and simultaneously induced cell apoptosis. However, resveratrol partially protected against oxLDL-induced CEC apoptosis. The oxLDL-induced alterations in levels of Bcl-2, Bax, and cytochrome c were completely normalized by resveratrol. Consequently, resveratrol partially decreased oxLDL-induced activation of caspases-9 and -3. Therefore, in this study, we show that resveratrol can protect against oxLDL-induced damage of the BBB through protecting disruption of the tight junction structure and apoptotic insults to CEC.
Lin
Yi-Ling
YL
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Wan Fang Hospital, Taipei, Taiwan.
Chang
Huai-Chia
HC
Chen
Ta-Liang
TL
Chang
Jin-Han
JH
Chiu
Wen-Ta
WT
Lin
Jia-Wei
JW
Chen
Ruei-Ming
RM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D051379:Mice; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D019108:Tight Junctions / Q000187:drug effects*
D008077:Lipoproteins, LDL; D013267:Stilbenes; C099252:oxidized low density lipoprotein; D000077185:Resveratrol