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Involvement of Peripheral-Type Benzodiazepine Receptors in the Intracellular Transport of Heme and Porphyrins1
Abstract
To investigate the involvement of peripheral-type benzodiazepine receptors (PBR) in heme metabolism, we examined the interaction of [55Fe]heme with PBR. Transfection of the cloned mouse PBR-isoquinoline carboxamide-binding protein (PBR/IBP) cDNA into monkey kidney Cos-1 cells resulted in a 2.5-fold increase in [55Fe]hemin binding sites, concomitant with the increase in [3H]PK11195 binding sites, as compared with those seen in antisense PBR/IBP cDNA-transfected cells. The binding of hemin to the transfected receptors exhibited a relatively high affinity with a Kd of 12 nM, and was inhibited by several benzodiazepine ligands, including PK11195, Ro 5-4864, diazepam and protoporphyrin IX. When mouse liver mitochondria were incubated with [55Fe]hemin, the binding to PBR had a Kd of 15 +/- 1.8 nM. The Bmax of [55Fe]hemin binding to the mitochondria was 6.88 +/- 0.76 pmol/mg of protein, a value consistent with that of [3H]PK11195 binding, with a lower affinity. Coproporphyrinogen III, a precursor porphyrin produced in the cytosol, is translocated into mitochondria, then is converted to protoporphyrinogen IX; this conversion decreased in the presence of benzodiazepine ligands. To examine whether this decrease was related to a decrease in the binding of coproporphyrinogen to the mitochondria, the effects of benzodiazepines on the binding of coproporphyrinogen were examined. As the binding was dose-dependently inhibited by PK11195, Ro 5-4864, and diazepam, porphyrins are likely to be endogenous ligands for PBR. We propose that PBR play a role in the intracellular transport of porphyrins and heme.
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“The product of this reaction – coproporphyrinogen III is transported to the intermembrane space of mitochondria probably by peripheral-type benzodiazepine receptors (PBR) [18,19].”
From Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer (2011) · cites this paper as [18]
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Metadata
- Authors
- Taketani, S., Kohno, H., Furukawa, T., & Tokunaga, R.
- Affiliations
- Kansai Medical University (JP)
- Corresponding author
- Taketani, Shigeru
- Venue
- The Journal of Biochemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 1995-04
- Volume
- 117
- Issue
- 4
- Pages
- 875-880
- ISSN
- 0021-924X (ISSN-L)
- 1756-2651
- OpenAlex
- W1702029570
- Cited by
- 123
- References
- 0
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 6 · 2015: 10 · 2014: 8 · 2013: 5 · 2012: 1
- FWCI
- 0.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- translocator protein (TSPO), heme transport, heme metabolism, PK11195, Ro5-4864, diazepam, protoporphyrin IX, coproporphyrinogen III, porphyrin synthesis
- MeSH terms
- Animals, Binding Sites, Biological Transport, Carrier Proteins, Cells, Cultured, Chlorocebus aethiops, Heme, Hemin, Intracellular Fluid, Iron, Iron Radioisotopes, Kidney, Mitochondria, Liver, Porphyrins, Protoporphyrins, Receptors, GABA-A, Transfection, Mice
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