title: In vitro mitochondrial effects of PK 11195, a synthetic translocator protein 18 kDa (TSPO) ligand, in human osteoblast-like cells.
abstract: The role of the TSPO in metabolism of human osteoblasts is unknown. We hypothesized that human osteoblast metabolism may be modulated by the TSPO. Therefore we evaluated the presence of TSPO in human osteoblast-like cells and the effect of its synthetic ligand PK 11195 on these cells. The presence of TSPO was determined by [(3)H]PK 11195 binding using Scatchard analysis: Bmax 7682 fmol/mg, Kd 9.24 nM. PK 11195 did not affect significantly cell proliferation, cell death, cellular viability, maturation, [(18)F]-FDG incorporation and hexokinase 2 gene expression or protein levels. PK 11195 exerted a suppressive effect on VDAC1 and caused an increase in TSPO gene expression or protein levels. In parallel there was an increase in mitochondrial mass, mitochondrial ATP content and a reduction in ΔΨm collapse. Thus, it appears that PK11195 (10(-5) M) stimulates mitochondrial activity in human osteoblast-like cells without affecting glycolytic activity and cell death.
authors: Department of Pharmacology, The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, POB 9649, Bat Galim, Haifa, 31096, Israel.
authors: Nahum
authors: N
authors: Rosenberg
authors: Orit
authors: O
authors: Rosenberg
authors: Abraham
authors: A
authors: Weizman
authors: Svetlana
authors: S
authors: Leschiner
authors: Yaakov
authors: Y
authors: Sakoury
authors: Fuad
authors: F
authors: Fares
authors: Michael
authors: M
authors: Soudry
authors: Gary
authors: G
authors: Weisinger
authors: Leo
authors: L
authors: Veenman
authors: Moshe
authors: M
authors: Gavish
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D006593:Hexokinase / Q000096:biosynthesis; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D010006:Osteoblasts; D018079:Receptors, GABA / Q000096:biosynthesis*; D050995:Voltage-Dependent Anion Channel 1 / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D007546:Isoquinolines; D024101:Mitochondrial Proteins; D018079:Receptors, GABA; C499229:TSPO protein, human; C494762:VDAC1 protein, human; D000255:Adenosine Triphosphate; D050995:Voltage-Dependent Anion Channel 1; D006593:Hexokinase; C037850:PK 11195