title: Peripheral benzodiazepine receptor regulates vascular endothelial activations via suppression of the voltage-dependent anion channel-1.
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.
authors.affiliation: Infectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Hee Kyoung
authors.initials: HK
authors.lastname: Joo
authors.forename: Yu Ran
authors.initials: YR
authors.lastname: Lee
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Lim
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Lee
authors.forename: Sunga
authors.initials: S
authors.lastname: Choi
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Cho
authors.forename: Myoung Soo
authors.initials: MS
authors.lastname: Park
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Ryoo
authors.forename: Jin Bong
authors.initials: JB
authors.lastname: Park
authors.forename: Byeong Hwa
authors.initials: BH
authors.lastname: Jeon
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D050995:Voltage-Dependent Anion Channel 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D018079:Receptors, GABA; C499229:TSPO protein, human; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D013482:Superoxide Dismutase; D050995:Voltage-Dependent Anion Channel 1