The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Targeted Disruption of the Peripheral-type Benzodiazepine Receptor Gene Inhibits Steroidogenesis in the R2C Leydig Tumor Cell Line
Open accessAbstract
To evaluate the role of the mitochondrial peripheral-type benzodiazepine receptor (PBR) in steroidogenesis, we developed a molecular approach based on the disruption of the PBR gene, by homologous recombination, in the constitutive steroid producing R2C rat Leydig tumor cell line. Inactivation of one allele of the PBR gene resulted in the suppression of PBR mRNA and ligand binding expression. Immunoblot and electron microscopic immunogold labeling analyses confirmed the absence of the 18-kDa PBR protein in the selected clone. Although mitochondria from the PBR-negative cells contained high levels of the constitutively expressed 30-kDa steroidogenic activity regulator protein, these cells produced minimal amounts of steroids compared with normal cells (5%). Moreover, mitochondria from PBR-negative cells failed to produce pregnenolone when supplied with exogenous cholesterol. Addition of the hydrosoluble cholesterol derivative, 22R-hydroxycholesterol, increased steroid production by the PBR-negative R2C cells, indicating that the cholesterol transport mechanism was impaired. Stable transfection of the PBR-negative R2C Leydig cells with a vector containing the PBR cDNA resulted in the recovery of the steroidogenic function of the cells. These data demonstrate that PBR is an indispensable element of the steroidogenic machinery, where it mediates the delivery of the substrate cholesterol to the inner mitochondrial side chain cleavage cytochrome P-450.
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Cites
Regulation of the acute production of steroids in steroidogenic cells
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Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis
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Self-citationArakane, F., Sugawara, T., Nishino, H., Liu, Z., Holt, J. A., Pain, D., Stocco, D. M., Miller, W. L., & Strauss, J. F. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13731 · Cited by 304
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Self-citationPon, L. A., & Orme-Johnson, N. R. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)84604-5 · Cited by 151
Cited by
Mechanisms Controlling the Function and Life Span of the Corpus Luteum
Niswender, G. D., Juengel, J. L., Silva, P. J., Rollyson, M. K., & McIntush, E. W. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.1.1 · Cited by 1,052
MAM (mitochondria-associated membranes) in mammalian cells: Lipids and beyond
Vance, J. E. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.11.014 · Cited by 625
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
Intracellular cholesterol transport
Liscum, L., & Munn, N. J. (1999) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/s1388-1981(99)00043-8 · Cited by 414
Rone, 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
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Metadata
- Authors
- Papadopoulos, V., Amri, H., Li, H., Boujrad, N., Vidic, B., & Garnier, M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-12
- Volume
- 272
- Issue
- 51
- Pages
- 32129-32135
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2134397312
- Cited by
- 219
- References
- 8
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Papadopoulos, V., Amri, H., Li, H., Boujrad, N., Vidic, B., & Garnier, M. (1997). Targeted Disruption of the Peripheral-type Benzodiazepine Receptor Gene Inhibits Steroidogenesis in the R2C Leydig Tumor Cell Line. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.272.51.32129
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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