Article ID Journal Published Year Pages File Type
2047824 FEBS Letters 2012 7 Pages PDF
Abstract

Peripheral benzodiazepine receptor (PBR) is a multifunctional protein mainly found on the outer mitochondrial membrane. PBR expression is increased by tumor necrosis factor-α (TNF-α) in endothelial cells. Adenoviral overexpression of PBR inhibits monocyte adhesion, VCAM-1, and ICAM-1 expression in TNF-α-activated endothelial cells. Rotenone, cyclosporine A, and bongkrekic acid suppress TNF-α-induced VCAM-1 expression. Overexpression of PBR inhibits voltage-dependent anion channel-1 (VDAC-1) expression and the silencing of PBR increases VDAC-1 expression in endothelial cells. Moreover, TNF-α-induced VCAM-1 expression is suppressed by VDAC-1 gene silencing. PBR overexpression significantly decreases TNF-α-induced mitochondrial reactive oxygen species and MnSOD expression. These results suggest that PBR can inhibit endothelial activation and this action is related to the inhibition of mitochondrial ROS and/or VDAC-1 expression in endothelial cells.

► Adenoviral overexpression of PBR inhibits monocyte adhesion, VCAM-1 and ICAM-1 expression in endothelial cells. ► PBR regulates voltage-dependent anion channel-1 expression. ► PBR overexpression significantly decreases mitochondrial reactive oxygen species. ► PBR can inhibit endothelial activation via inhibition of VDAC-1 expression and/or reactive oxygen species.

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