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.

Ischemic Neurodegeneration in Stroke-Prone Spontaneously Hypertensive Rats and Its Prevention with Antioxidants Such as Polyphenols

“…Moreover, they demonstrated decreased levels of plasma endothelin-1 and NO, which are increased by hypercholesterolemia. On the other hand, it was also shown that resveratrol protects against injury to the BBB caused by oxidized LDL (oxLDL) (Lin et al, 2010). It is considered that the mechanism behind these effects of resveratrol involves amelioration of the effects of oxLDL on the expression of occludin and ZO-1, which aids the stability of tight junctions.…”

Neuron-derived orphan receptor 1 transduces survival signals in neuronal cells in response to hypoxia-induced apoptotic insults

“…A change in morphology, DNA damage, and cell cycle arrest are characteristic features of cells undergoing apoptosis. 13,21,35 In addition, OGD activated caspase-3 in neuro-2a cells. Caspase-3 plays a key role in triggering intrinsic and extrinsic cell apoptosis.…”

“…When cells undergo apoptosis, specific apoptotic characteristics may appear, including a changed morphology, caspase cascade activation, DNA fragmentation, and cell cycle arrest at the sub-G 1 phase. 21,35 In neuronal development, because apoptosis can precisely regulate the programmed natural death of neurons, it is thought to play important roles in neurogenesis. 14,29 However, premature or irregular apoptotic regulation can lead to the pathogenesis of neurodegeneration, subsequently leading to various acute or chronic brain diseases.…”

Resveratrol (3,5,4′-trihydroxystilbene) and its properties in oral diseases

“…Polyphenols are hydrophobic scaffolds exhibiting poor absorption and solubility, resulting in the very short half-life of RSV in the circulatory system (58). Presence of the glycosylated form of RSV is considered to improve physicochemical properties, such as solubility and partition coefficient in order to facilitate the entry of polyphenols into enterocytes (59) and improve bioavailability (60).…”