|
|
Previous Article | Table of Contents | Next Article 
Involvement of peripheral benzodiazepine receptors in the protection of
hematopoietic cells against oxygen radical damage
P Carayon, M Portier, D Dussossoy, A Bord, G Petitpretre, X Canat, G Le Fur and P Casellas
Department of Immunology, Sanofi Recherche, Montpelier, France.
Several putative functions have been attributed to the peripheral
benzodiazepine receptor (PBR), but its precise physiologic role has not
been elucidated. In the present study, we investigated PBR function by
quantifying this receptor in leukocyte subsets from healthy donors and in
leukemic blasts from lymphoid and myeloid lineages. Using a monoclonal
antibody (MoAb) directed against the human PBR and a quantitative flow
cytometric assay, we found that phagocytic cells from healthy donors
displayed a higher level of PBRs than lymphocytes or natural killer (NK)
cells. Among the lymphoid lineage, thymocytes and IgD-negative B cells
expressed the lowest levels. However, because of the wide heterogeneity of
PBR levels among 42 acute or chronic lymphoid and myeloid leukemias, it was
not possible to assign PBR expression to a stage of maturation or a cell
lineage. Although the PBR displayed a mitochondrial subcellular
localization, its expression was not correlated with the mitochondrial
content, suggesting a modulation of PBR density at the level of the
mitochondria. This modulation was confirmed when we studied in detail the
PBR expression during T-cell development by both flow cytometry and
confocal microscopy. We found that the PBR was expressed with a bimodal
profile during T-cell development, identical to the one observed with the
proto-oncogene, Bcl- 2. The high similarity in the expression of both the
PBR and the Bcl-2 proto-oncogene in T-cell and B-cell subsets, their common
mitochondrial localization, and the observation of high quantities of PBR
in phagocytic cells, which are known to produce high levels of radical
oxygen species, suggested that PBRs may participate in an antioxidant
pathway. Indeed, a strong correlation was established between the ability
of hematopoietic cell lines to resist H202 cytotoxicity and their level of
PBR expression. Demonstration of the role of PBR in the protection against
H202 was obtained by transfecting JURKAT cells with the human PBR cDNA.
Transfected cells exhibited increased resistance to H202 compared with
wild-type cells, suggesting that PBR may prevent mitochondria from radical
damages and thereby modulate apoptosis in the hematopoietic system.
Volume 87,
Issue 8,
pp. 3170-3178,
04/15/1996
Copyright © 1996 by The American Society of Hematology

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
F. Favreau, L. Rossard, K. Zhang, T. Desurmont, E. Manguy, A. Belliard, S. Fabre, J. Liu, Z. Han, R. Thuillier, et al.
Expression and modulation of translocator protein and its partners by hypoxia reoxygenation or ischemia and reperfusion in porcine renal models
Am J Physiol Renal Physiol,
July 1, 2009;
297(1):
F177 - F190.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Milani, A. Lundmark, J. Nordlund, A. Kiialainen, T. Flaegstad, G. Jonmundsson, J. Kanerva, K. Schmiegelow, K. L. Gunderson, G. Lonnerholm, et al.
Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation
Genome Res.,
January 1, 2009;
19(1):
1 - 11.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. F. Santidrian, A. M. Cosialls, L. Coll-Mulet, D. Iglesias-Serret, M. de Frias, D. M. Gonzalez-Girones, C. Campas, A. Domingo, G. Pons, and J. Gil
The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells
Haematologica,
December 1, 2007;
92(12):
1631 - 1638.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. N. Obame, R. Zini, R. Souktani, A. Berdeaux, and D. Morin
Peripheral Benzodiazepine Receptor-Induced Myocardial Protection is Mediated by Inhibition of Mitochondrial Membrane Permeabilization
J. Pharmacol. Exp. Ther.,
October 1, 2007;
323(1):
336 - 345.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Costa, A. Salvetti, L. Rossi, F. Spinetti, A. Lena, B. Chelli, M. Rechichi, E. Da Pozzo, V. Gremigni, and C. Martini
Peripheral Benzodiazepine Receptor: Characterization in Human T-Lymphoma Jurkat Cells
Mol. Pharmacol.,
January 1, 2006;
69(1):
37 - 44.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. B. Walter, J. L. Pirga, M. R. Cronk, S. Mayer, F. R. Appelbaum, and D. E. Banker
PK11195, a peripheral benzodiazepine receptor (pBR) ligand, broadly blocks drug efflux to chemosensitize leukemia and myeloma cells by a pBR-independent, direct transporter-modulating mechanism
Blood,
November 15, 2005;
106(10):
3584 - 3593.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
O. R. Kunduzova, G. Escourrou, F. De La Farge, R. Salvayre, M.-H. Seguelas, N. Leducq, F. Bono, J.-M. Herbert, and A. Parini
Involvement of Peripheral Benzodiazepine Receptor in the Oxidative Stress, Death-Signaling Pathways, and Renal Injury Induced by Ischemia-Reperfusion
J. Am. Soc. Nephrol.,
August 1, 2004;
15(8):
2152 - 2160.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Galiegue, P. Casellas, A. Kramar, N. Tinel, and J. Simony-Lafontaine
Immunohistochemical Assessment of the Peripheral Benzodiazepine Receptor in Breast Cancer and Its Relationship with Survival
Clin. Cancer Res.,
March 15, 2004;
10(6):
2058 - 2064.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Leducq, F. Bono, T. Sulpice, V. e. Vin, P. Janiak, G. L. Fur, S. E. O'Connor, and J.-M. Herbert
Role of Peripheral Benzodiazepine Receptors in Mitochondrial, Cellular, and Cardiac Damage Induced by Oxidative Stress and Ischemia-Reperfusion
J. Pharmacol. Exp. Ther.,
September 1, 2003;
306(3):
828 - 837.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Everett, M. Barry, X. Sun, S. F. Lee, C. Frantz, L. G. Berthiaume, G. McFadden, and R. C. Bleackley
The Myxoma Poxvirus Protein, M11L, Prevents Apoptosis by Direct Interaction with the Mitochondrial Permeability Transition Pore
J. Exp. Med.,
November 4, 2002;
196(9):
1127 - 1140.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. P. Faure, T. Hauet, Z. Han, J. M. Goujon, I. Petit, G. Mauco, M. Eugene, M. Carretier, and V. Papadopoulos
Polyethylene Glycol Reduces Early and Long-Term Cold Ischemia-Reperfusion and Renal Medulla Injury
J. Pharmacol. Exp. Ther.,
September 1, 2002;
302(3):
861 - 870.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Ferzaz, E. Brault, G. Bourliaud, J.-P. Robert, G. Poughon, Y. Claustre, F. Marguet, P. Liere, M. Schumacher, J.-P. Nowicki, et al.
SSR180575 (7-Chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide), a Peripheral Benzodiazepine Receptor Ligand, Promotes Neuronal Survival and Repair
J. Pharmacol. Exp. Ther.,
June 1, 2002;
301(3):
1067 - 1078.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Bribes, P. Casellas, H. Vidal, D. Dussossoy, and D. Casellas
Peripheral Benzodiazepine Receptor Mapping in Rat Kidney. Effects of Angiotensin II-Induced Hypertension
J. Am. Soc. Nephrol.,
January 1, 2002;
13(1):
1 - 9.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Johnston, W. Jiang, T. Chu, and B. Levine
Identification of Genes Involved in the Host Response to Neurovirulent Alphavirus Infection
J. Virol.,
November 1, 2001;
75(21):
10431 - 10445.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A.-S. Belzacq, E. Jacotot, H. L. A. Vieira, D. Mistro, D. J. Granville, Z. Xie, J. C. Reed, G. Kroemer, and C. Brenner
Apoptosis Induction by the Photosensitizer Verteporfin: Identification of Mitochondrial Adenine Nucleotide Translocator as a Critical Target
Cancer Res.,
February 1, 2001;
61(4):
1260 - 1264.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
H. Li, Z.-x. Yao, B. Degenhardt, G. Teper, and V. Papadopoulos
Cholesterol binding at the cholesterol recognition/ interaction amino acid consensus (CRAC) of the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by an HIV TAT-CRAC peptide
PNAS,
January 23, 2001;
(2001)
31461598.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
A. Mazzone, I. Mazzucchelli, M. Vezzoli, E. Ottini, C. Auguadro, A. Serio, and C. Falcone
Increased expression of peripheral benzodiazepine receptors on leukocytes in silent myocardial ischemia
J. Am. Coll. Cardiol.,
September 1, 2000;
36(3):
746 - 750.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Costantini, E. Jacotot, D. Decaudin, and G. Kroemer
Mitochondrion as a Novel Target of Anticancer Chemotherapy
J Natl Cancer Inst,
July 5, 2000;
92(13):
1042 - 1053.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Galiegue, O. Jbilo, T. Combes, E. Bribes, P. Carayon, G. Le Fur, and P. Casellas
Cloning and Characterization of PRAX-1. A NEW PROTEIN THAT SPECIFICALLY INTERACTS WITH THE PERIPHERAL BENZODIAZEPINE RECEPTOR
J. Biol. Chem.,
January 29, 1999;
274(5):
2938 - 2952.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. S. Wadia, R. M. E. Chalmers-Redman, W. J. H. Ju, G. W. Carlile, J. L. Phillips, A. D. Fraser, and W. G. Tatton
Mitochondrial Membrane Potential and Nuclear Changes in Apoptosis Caused by Serum and Nerve Growth Factor Withdrawal: Time Course and Modification by (-)-Deprenyl
J. Neurosci.,
February 1, 1998;
18(3):
932 - 947.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. J. Donohue
Eubacterial signal transduction by ligands of the mammalian peripheral benzodiazepine receptor complex
PNAS,
May 13, 1997;
94(10):
4821 - 4822.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Li, Z.-x. Yao, B. Degenhardt, G. Teper, and V. Papadopoulos
Cholesterol binding at the cholesterol recognition/ interaction amino acid consensus (CRAC) of the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by an HIV TAT-CRAC peptide
PNAS,
January 30, 2001;
98(3):
1267 - 1272.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|