Induction of peripheral-type benzodiazepine receptors during differentiation of mouse erythroleukemia cells. A possible involvement of these receptors in heme biosynthesis.
Open accessAbstract
To search for a possible role for peripheral-type benzodiazepine receptors (PBR) during erythroid differentiation, we cloned the PBR isoquinoline carboxamide-binding protein (PBR/IBP), an 18-kDa protein on PBR, from a mouse erythroleukemia (MEL) cell cDNA library. Sequence analysis revealed that PBR/IBP comprises 169 amino acid residues (M(r) 18,828), and has a high homology with PBR/IBP from other sources. The cDNA allows for the expression of active PBR/IBP, exhibiting a high affinity for isoquinoline carboxamide, [3H]PK11195, with Kd of 0.80 and 1.56 nM. RNA blot analysis revealed that treatment of MEL cells with dimethyl sulfoxide led to an increase in PBR/IBP mRNA (delta 1.0 kilobases) for up to 72 h, with a concomitant induction of mRNAs for heme biosynthetic enzymes, coproporphyrinogen oxidase and ferrochelatase. The induction of PBR/IBP mRNA was also observed in MEL cells induced with diazepam. The binding activity of [3H]PK11195 in MEL cells showed a high affinity with Kd of 0.69-2.13 nM, and increased during erythroid differentiation. The order of potency of different ligands to compete against [3H]PK11195 binding in induced MEL cells was PK11195 > protoporphyrin IX > diazepam > coproporphyrinogen III > coproporphyrin III > estazolam. In contrast to the induction of PBR/IBP in induced MEL cells, the voltage-dependent anion channel (mitochondrial porin) associated with PBR remained unchanged. These results suggest that PBR/IBP on PBR may be involved in porphyrin transport and may even be a critical factor in erythroid-specific induction of heme biosynthesis.
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The product coproporphyrinogen III is transported to the intermembrane space of mitochondria probably by peripheral-type benzodiazepine receptors (PBR).
“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 [19]
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- Authors
- Taketani, S., Kohno, H., Okuda, M., Furukawa, T., & Tokunaga, R.
- Affiliations
- Kansai Medical University (JP)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1994-03
- Volume
- 269
- Issue
- 10
- Pages
- 7527-7531
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1526937427
- Cited by
- 88
- References
- 32
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 3 · 2018: 1 · 2017: 2 · 2016: 5 · 2015: 6 · 2014: 3 · 2013: 1 · 2012: 2
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- translocator protein (TSPO), erythroid differentiation, mouse erythroleukemia cells, heme biosynthesis, coproporphyrinogen oxidase, ferrochelatase, diazepam, dimethyl sulfoxide, cDNA cloning, ligand specificity
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Cloning, Molecular, Coproporphyrinogen Oxidase, Leukemia, Erythroblastic, Acute, Ferrochelatase, Hematopoiesis, Heme, Isoquinolines, Molecular Sequence Data, Receptors, GABA-A, RNA, Messenger, Tumor Cells, Cultured, Blotting, Western, DNA, Complementary, Mice
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