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.

Links

Publisher Full Text

Authors

Joo HK, Lee YR, Lim SY, Lee EJ, Choi S, Cho EJ, Park MS, Ryoo S, Park JB, Jeon BH

Institution

Infectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.

Source

FEBS letters 586:9 2012 May 7 pg 1349-55

MeSH

Adenoviridae
Cell Adhesion
Cytokines
Down-Regulation
Endothelial Cells
Human Umbilical Vein Endothelial Cells
Humans
Intercellular Adhesion Molecule-1
Mitochondria
Monocytes
Reactive Oxygen Species
Receptors, GABA
Superoxide Dismutase
Tumor Necrosis Factor-alpha
Up-Regulation
Vascular Cell Adhesion Molecule-1
Voltage-Dependent Anion Channel 1

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22616995