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Biochemistry (Moscow)

, Volume 74, Issue 4, pp 421–429 | Cite as

Effect of peripheral benzodiazepine receptor (PBR/TSPO) ligands on opening of Ca2+-induced pore and phosphorylation of 3.5-kDa polypeptide in rat brain mitochondria

  • O. V. Krestinina
  • D. E. Grachev
  • I. V. Odinokova
  • G. Reiser
  • Yu. V. Evtodienko
  • T. S. AzarashviliEmail author
Article

Abstract

The effect of nanomolar concentrations of PBR/TSPO ligands—Ro 5-4864, PK11195, and PPIX—on Ca2+-induced permeability transition pore (PTP) opening in isolated rat brain mitochondria was investigated. PBR/TSPO agonist Ro 5-4864 (100 nM) and endogenous ligand PPIX (1 μM) were shown to stimulate PTP opening, while antagonist PK11195 (100 nM) suppressed this process. Correlation between PBR ligand action on PTP opening and phosphorylation of a 3.5 kDa polypeptide was investigated. In intact brain mitochondria, incorporation of [γ-32P]ATP into 3.5 kDa peptide was decreased in the presence of Ro 5-4864 and PPIX and increased in the presence of PK11195. At threshold Ca2+ concentrations leading to PTP opening, PBR/TSPO ligands were found to stimulate dephosphorylation of the 3.5 kDa peptide. Specific anti-PBR/TSPO antibody prevented both PTP opening and dephosphorylation of the 3.5-kDa peptide. The peptide was identified as subunit c of FoF1-ATPase by Western blot using specific anti-subunit c antibody. The results suggest that subunit c of FoF1-ATPase could be an additional target for PBR/TSPO ligands action, is subjected to Ca2+- and TSPO-dependent phosphorylation/dephosphorylation, and is involved in PTP operation in mitochondria.

Key words

brain mitochondria peripheral benzodiazepine receptor permeability transition pore FoF1-ATPase subunit c PBR/TSPO 

Abbreviations

ANT

adenine nucleotide translocator

CsA

cyclosporin A

IBP

isoquinoline-binding protein

PBR

peripheral benzodiazepine receptor

PBR/TSPO

translocator protein of peripheral benzodiazepine receptor

PK11195

1-(2-chlorophenyl-N-methylpropyl)-3-isoquinoline carboxamide

PKA

protein kinase A

PPIX

protoporphyrin IX

PTP

permeability transition pore (non-selective Ca2+-induced mitochondrial pore)

Ro 5-4864

7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepine

TPP+

tetraphenylphosphonium cation

VDAC

voltage-dependent anion channel

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Copyright information

© Pleiades Publishing, Ltd. 2009

Authors and Affiliations

  • O. V. Krestinina
    • 1
  • D. E. Grachev
    • 1
  • I. V. Odinokova
    • 1
  • G. Reiser
    • 2
  • Yu. V. Evtodienko
    • 1
  • T. S. Azarashvili
    • 1
    Email author
  1. 1.Institute of Theoretical and Experimental BiophysicsRussian Academy of SciencesPushchino, Moscow RegionRussia
  2. 2.Department of MedicineInstitute of Neurobiochemistry, Otto-von-Guericke UniversityMagdeburgGermany

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