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In vitro mitochondrial effects of PK 11195, a synthetic translocator protein 18 kDa (TSPO) ligand, in human osteoblast-like cells

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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 [3H]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, [18F]-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.

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Authors and Affiliations

  1. Department of Pharmacology, The Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, POB 9649, Bat Galim, Haifa, 31096, Israel

    Nahum Rosenberg, Orit Rosenberg, Svetlana Leschiner, Yaakov Sakoury, Fuad Fares, Michael Soudry, Leo Veenman & Moshe Gavish

  2. Orthopaedics A Department, Rambam Medical Center, Haifa, Israel

    Nahum Rosenberg & Michael Soudry

  3. Research Unit, Geha Mental Health Center and the Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Abraham Weizman

  4. Department of Endocrinology, Metabolism and Hypertension, Tel Aviv University Sourasky Medical Center, Tel Aviv, Israel

    Gary Weisinger

Authors
  1. Nahum Rosenberg
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  2. Orit Rosenberg
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  3. Abraham Weizman
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  4. Svetlana Leschiner
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  5. Yaakov Sakoury
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  6. Fuad Fares
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  7. Michael Soudry
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  8. Gary Weisinger
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  9. Leo Veenman
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  10. Moshe Gavish
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Correspondence to Moshe Gavish.

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Nahum Rosenberg and Orit Rosenberg had equal contribution

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Rosenberg, N., Rosenberg, O., Weizman, A. et al. In vitro mitochondrial effects of PK 11195, a synthetic translocator protein 18 kDa (TSPO) ligand, in human osteoblast-like cells. J Bioenerg Biomembr 43, 739–746 (2011). https://doi.org/10.1007/s10863-011-9388-x

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  • DOI: https://doi.org/10.1007/s10863-011-9388-x

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