Apoptosis

, Volume 10, Issue 1, pp 91–104

Evidence in favour of a role for peripheral-type benzodiazepine receptor ligands in amplification of neuronal apoptosis

  • E. G. Jordà
  • A. Jiménez
  • E. Verdaguer
  • A. M. Canudas
  • J. Folch
  • F. X. Sureda
  • A. Camins
  • M. Pallàs
Article
  • 117 Downloads

Abstract

The mitochondrial peripheral benzodiazepine receptor (PBR) is involved in a functional structure designated as the mitochondrial permeability transition (MPT) pore, which controls apoptosis. PBR expression in nervous system has been reported in glial and immune cells. We now show expression of both PBR mRNA and protein, and the appearance of binding of a synthetic ligand fluo-FGIN-1-27 in mitochondria of rat cerebellar granule cells (CGCs). Additionally, the effect of PBR ligands on colchicine-induced apoptosis was investigated. Colchicine-induced neurotoxicity in CGCs was measured at 24 h. We show that, in vitro, PBR ligands 1-(2-chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195), 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4- benzodiazepin-2-one (Ro5-4864) and diazepam (25– 50 μM) enhanced apoptosis induced by colchicine, as demonstrated by viability experiments, flow cytometry and nuclear chromatin condensation. Enhancement of colchicine-induced apoptosis was characterized by an increase in mitochondrial release of cytochrome c and AIF proteins and an enhanced activation of caspase-3, suggesting mitochondrion dependent mechanism that is involved in apoptotic process. Our results indicate that exposure of neural cells to PBR ligands generates an amplification of apoptotic process induced by colchicine and that the MPT pore may be involved in this process.

Keywords:

AIF cerebellar granule cells colchicine Cyt c mitochondrial permeability transition peripheral benzodiazepine receptor 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • E. G. Jordà
    • 1
  • A. Jiménez
    • 1
  • E. Verdaguer
    • 1
  • A. M. Canudas
    • 1
  • J. Folch
    • 2
  • F. X. Sureda
    • 2
  • A. Camins
    • 1
  • M. Pallàs
    • 1
  1. 1.Unitat de Farmacologia i Farmacognòsia, Facultat de FarmàciaUniversitat de Barcelona, Nucli Universitari de PedralbesBarcelonaSpain
  2. 2.Unitat de Farmacologia and Unitat de Bioquímica, Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain
  3. 3.Unitat de Farmacologia i Farmacognòsia, Facultat de FarmàciaUniversitat de Barcelona, Nucli Universitari de PedralbesBarcelonaSpain

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