title: 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.
abstract: 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.
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Lin
authors.forename: Huai-Chia
authors.initials: HC
authors.lastname: Chang
authors.forename: Ta-Liang
authors.initials: TL
authors.lastname: Chen
authors.forename: Jin-Han
authors.initials: JH
authors.lastname: Chang
authors.forename: Wen-Ta
authors.initials: WT
authors.lastname: Chiu
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Lin
authors.forename: Ruei-Ming
authors.initials: RM
authors.lastname: Chen
mesh_terms: 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*
chemical_list: D008077:Lipoproteins, LDL; D013267:Stilbenes; C099252:oxidized low density lipoprotein; D000077185:Resveratrol