In vivo and in vitro peripheral-type benzodiazepine receptor polymerization: functional significance in drug ligand and cholesterol binding
Abstract
Peripheral-type benzodiazepine receptor (PBR) is an 18 kDa high-affinity drug ligand and cholesterol binding protein involved in various cell functions. Antisera for distinct PBR areas identified immunoreactive proteins of 18, 40, and 56 kDa and occasionally 72, 90, and 110 kDa in testicular Leydig and breast cancer cells. These sizes may correspond to PBR polymers and correlated to the levels of reactive oxygen species. Treatment of Leydig cells with human chorionic gonadotropin rapidly induced free radical, PBR polymer, and steroid formation. UV photoirradiation generates ROS species, which increased the size of intramembraneous particles of recombinant PBR reconstituted into proteoliposomes consistent with polymer formation, determined both by SDS-PAGE and by freeze-fracture electron microscopy. Spectroscopic analysis revealed the formation of dityrosines as the covalent cross-linker between PBR monomers. Moreover, photoirradiation increased PK 11195 drug ligand binding and reduced cholesterol binding capacity of proteoliposomes. Further addition of PK 11195 drug ligand to polymers increased the rate of cholesterol binding. These data indicate that reactive oxygen species induce in vivo and in vitro the formation of covalent PBR polymers. We propose that the PBR polymer might be the functional unit responsible for ligand-activated cholesterol binding and that PBR polymerization is a dynamic process modulating the function of this receptor in cholesterol transport and other cell-specific PBR-mediated functions.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Hormonal stimulation of steroidogenesis in a steroidogenic cell model resulted in increased TSPO polymerization in correlation with increased ligand-binding affinity and steroid production.
“Hormonal stimulation of steroidogenesis in a steroidogenic cell model resulted in increased TSPO polymerization in correlation with increased ligand-binding affinity and steroid production (123, 124).”
From Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies (2016) · cites this paper as [124]
Cites
Enigma of the peripheral benzodiazepine receptor
Gavish, M., Bachman, I., Shoukrun, R., Katz, Y., Veenman, L., Weisinger, G., & Weizman, A. (1999) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01424-8 · Cited by 512 · see citing works
In vitro studies on the role of the peripheral-type benzodiazepine receptor in steroidogenesis
Culty, M., Li, H., Boujrad, N., Amri, H., Vidic, B., Bernassau, J. M., Reversat, J. L., & Papadopoulos, V (1999) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(99)00056-4 · Cited by 122 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Rupprecht, R., Papadopoulos, V., Rammes, G., Baghai, T. C., Fan, J., Akula, N., Groyer, G., Adams, D., & Schumacher, M. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3295 · Cited by 930 · see citing works
Self-citationRone, M. B., Fan, J., & Papadopoulos, V. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.03.001 · Cited by 399 · see citing works
Self-citationLacapère, J.-J., & Papadopoulos, V. (2003) · Steroids · doi:10.1016/s0039-128x(03)00101-6 · Cited by 342 · see citing works
Self-citationRone, M. B., Midzak, A. S., Issop, L., Rammouz, G., Jagannathan, S., Fan, J., Ye, X., Blonder, J., Veenstra, T., & Papadopoulos, V. (2012) · Molecular Endocrinology · doi:10.1210/me.2012-1159 · Cited by 247 · see citing works
Self-citationHauet, T., Yao, Z.-X., Bose, H. S., Wall, C. T., Han, Z., Li, W., Hales, D. B., Miller, W. L., Culty, M., & Papadopoulos, V. (2005) · Molecular Endocrinology · doi:10.1210/me.2004-0307 · Cited by 252 · see citing works
Self-citationProtein-protein interactions mediate mitochondrial cholesterol transport and steroid biosynthesis
Liu, J., Rone, M. B., & Papadopoulos, V. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608820200 · Cited by 241 · see citing works
Self-citationAdrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies
Midzak, A., & Papadopoulos, V. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00106 · Cited by 114 · see citing works
Self-citationThe tspo-nox1 axis controls phagocyte-triggered pathological angiogenesis in the eye
Wolf, A., Herb, M., Schramm, M., & Langmann, T. (2020) · Nature Communications · doi:10.1038/s41467-020-16400-8 · Cited by 80 · see citing works
In Vivo TSPO Signal and Neuroinflammation in Alzheimer’s Disease
Tournier, B. B., Tsartsalis, S., Ceyzériat, K., Garibotto, V., & Millet, P. (2020) · Cells · doi:10.3390/cells9091941 · Cited by 79 · see citing works
Colasanti, A., Owen, D. R., Grozeva, D., Rabiner, E. A., Matthews, P. M., Craddock, N., & Young, A. H. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.07.007 · Cited by 55 · see citing works
Role of Mitochondria in Steroidogenesis
Miller, W. L. (2011) · Endocrine Development · doi:10.1159/000321204 · Cited by 57 · see citing works
Midzak, A., & Papadopoulos, V. (2014) · Traffic · doi:10.1111/tra.12177 · Cited by 38 · see citing works
Self-citationMidzak, A. S., Akula, N., Rone, M. B., & Papadopoulos, V. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.03.023 · Cited by 20 · see citing works
Self-citation
- Authors
- Delavoie, F., Li, H., Hardwick, M., Robert, J.-C., Giatzakis, C., Péranzi, G., Yao, Z.-X., Maccario, J., Lacapère, J.-J., & Papadopoulos, V.
- Affiliations
- Inserm (FR)
- Division of Hormone Research, Departments of Cell Biology and of Pharmacology and Neurosciences, Georgetown University Medical Center, Washington, D.C. 20057, Unité INSERM U410, Faculté de Médecine Xavier Bichat, 16 Rue Henri Huchard, 75870 Paris Cedex 18, France, and Unité INSERM U472, 16 Avenue Paul Vaillant-Couturier, Batiment INSERM, 94807 Villejuif, France
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2003-03-25
- Volume
- 42
- Issue
- 15
- Pages
- 4506-4519
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W2011341002
- Cited by
- 168
- References
- 2
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 11 · 2020: 9 · 2019: 3 · 2018: 8 · 2017: 7 · 2016: 7 · 2015: 16 · 2014: 12 · 2013: 4 · 2012: 14
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Environmental Health Sciences (R01ES007747, ES 07747)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- translocator protein (TSPO), reactive oxygen species, dityrosine cross-linking, cholesterol binding, proteoliposomes, Leydig cells, human chorionic gonadotropin, free radical generation, cholesterol transport
- MeSH terms
- Animals, Cholesterol, Ligands, Protein Binding, Proteolipids, Receptors, GABA-A, Spectrophotometry, Ultraviolet Rays, Reactive Oxygen Species, Dimerization, Mice, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
