title: The 18-kDa Translocator Protein Inhibits Vascular Cell Adhesion Molecule-1 Expression via Inhibition of Mitochondrial Reactive Oxygen Species.
abstract: Translocator protein 18 kDa (TSPO) is a mitochondrial outer membrane protein and is abundantly expressed in a variety of organ and tissues. To date, the functional role of TSPO on vascular endothelial cell activation has yet to be fully elucidated. In the present study, the phorbol 12-myristate 13-acetate (PMA, 250 nM), an activator of protein kinase C (PKC), was used to induce vascular endothelial activation. Adenoviral TSPO overexpression (10-100 MOI) inhibited PMA-induced vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) expression in a dose dependent manner. PMA-induced VCAM-1 expressions were inhibited by Mito-TEMPO (0.1-0.5 μM), a specific mitochondrial antioxidants, and cyclosporin A (1-5 μM), a mitochondrial permeability transition pore inhibitor, implying on an important role of mitochondrial reactive oxygen species (ROS) on the endothelial activation. Moreover, adenoviral TSPO overexpression inhibited mitochondrial ROS production and manganese superoxide dismutase expression. On contrasts, gene silencing of TSPO with siRNA increased PMA-induced VCAM-1 expression and mitochondrial ROS production. Midazolam (1-50 μM), TSPO ligands, inhibited PMA-induced VCAM-1 and mitochondrial ROS production in endothelial cells. These results suggest that mitochondrial TSPO can inhibit PMA-induced endothelial inflammation via suppression of VCAM-1 and mitochondrial ROS production 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 301-747, Korea.
authors.forename: Hee Kyoung
authors.initials: HK
authors.lastname: Joo
authors.affiliation: Infectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Korea.
authors.forename: Yu Ran
authors.initials: YR
authors.lastname: Lee
authors.affiliation: Infectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Korea.
authors.forename: Gun
authors.initials: G
authors.lastname: Kang
authors.affiliation: Infectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Korea.
authors.forename: Sunga
authors.initials: S
authors.lastname: Choi
authors.affiliation: Infectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Korea.
authors.forename: Cuk-Seong
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Korea.
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Ryoo
authors.affiliation: Infectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Korea.
authors.forename: Jin Bong
authors.initials: JB
authors.lastname: Park
authors.affiliation: Infectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Korea.
authors.forename: Byeong Hwa
authors.initials: BH
authors.lastname: Jeon
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C573420:ICAM1 protein, human; D017382:Reactive Oxygen Species; D018079:Receptors, GABA; C499229:TSPO protein, human; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016572:Cyclosporine; D013755:Tetradecanoylphorbol Acetate
keywords: PKC; ROS; TSPO; VCAM-1; endothelial cells