Peripheral benzodiazepine receptor regulates vascular endothelial activations via suppression of the voltage-dependent anion channel-1

Hee Kyoung Joo; Yu Ran Lee; Sun Young Lim; Eun Ji Lee; Sunga Choi; Eun Jung Cho; Myoung Soo Park; Sungwoo Ryoo; Jin Bong Park; Byeong Hwa Jeon

doi:10.1016/j.febslet.2012.03.049

Peripheral benzodiazepine receptor regulates vascular endothelial activations via suppression of the voltage-dependent anion channel-1

FEBS Lett. 2012 May 7;586(9):1349-55. doi: 10.1016/j.febslet.2012.03.049. Epub 2012 Mar 31.

Authors

Hee Kyoung Joo¹, Yu Ran Lee, Sun Young Lim, Eun Ji Lee, Sunga Choi, Eun Jung Cho, Myoung Soo Park, Sungwoo Ryoo, Jin Bong Park, Byeong Hwa Jeon

Affiliation

¹ Infectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.

PMID: 22616995
DOI: 10.1016/j.febslet.2012.03.049

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.

Publication types

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

MeSH terms

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

Substances

Cytokines
Reactive Oxygen Species
Receptors, GABA
TSPO protein, human
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1
Intercellular Adhesion Molecule-1
Superoxide Dismutase
Voltage-Dependent Anion Channel 1