Peripheral benzodiazepine receptor(PBR) is a multi functional protein mainly found on the outer mitochon drial membrane. PBR expression is increased by tumor necrosis factor-a(TNF-a) in endothelial cells.
Rotenone, cyclosporine A, and bongkrekic acid suppress TNF-a-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-a-induced VACM-1 expression is suppressed by VDAC-1 gene silencing. PBR Overexpression significanfly decreases TNF-a-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 mitochon drial ROS and/or VDAC-1 expression in endothelial cells.