Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mitochondrial benzodiazepine receptor (mBzR) has been solubilized with retention of reversible ligand binding, and the associated subunits were characterized. mBzR comprises immunologically distinct protein subunits of 18-, 30-, and 32-kDa. The 18-kDa protein is labeled by the isoquinoline carboxamide mBzR ligand [3H]PK14105, whereas the 30- and 32-kDa subunits are labeled by the benzodiazepine (Bz) ligands [3H]flunitrazepam and [3H]AHN-086. Selective antibodies and reagents identify the 32- and 30-kDa proteins as the voltage-dependent anion channel (VDAC) and the adenine nucleotide carrier (ADC), respectively. While isoquinoline carboxamide and Bz ligands target different subunits, they interact allosterically, as the binding of Bz and isoquinoline carboxamide ligands is mutually competitive at low nanomolar concentrations. Moreover, eosin-5-maleimide and mercuric chloride inhibit [3H]PK11195 binding to the intact receptor via sulfhydryl groups that are present in ADC. VDAC and ADC, outer and inner mitochondrial membrane channel proteins, respectively, together with the 18-kDa subunit, may comprise mBzR at functionally important transport sites at the junction of two mitochondrial membranes.
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PMID:Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier. 137 86

The purified mitochondrial benzodiazepine receptor (mBzR) is a complex comprising the voltage-dependent anion channel (VDAC), adenine nucleotide carrier, and an 18-kDa protein that binds isoquinoline carboxamide ligands (McEnery, M. W., Snowman, A. M., Trifiletti, R. R., and Snyder, S. H. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 3170-3174). An antiserum raised against the mBzR complex reacts selectively with VDAC and is used, along with purification, electrophysiological and immunohistochemical techniques, to characterize the properties and distribution of rat brain VDAC. Although purified VDAC displays biochemical and electrical conductance properties similar to VDAC from other sources, the immunohistochemical distribution of VDAC in rat brain is heterogeneous with pronounced regional variations; the pontine nuclei, the supraoptic nucleus, Purkinje cells of the cerebellum, and the caudate putamen evidence the highest density. The distribution of VDAC is inclusive of the more discretely localized 18-kDa mBzR protein, suggesting that only a portion of the total VDAC participates in the mBzR. The histochemical localizations of the mitochondrial marker enzymes glutamate dehydrogenase and cytochrome c oxidase also indicate marked regional variability in both mitochondrial content and composition. The discrete expression of VDAC reflects a striking heterogeneity of rat brain mitochondria and underlying differences in the utilization of mitochondrial outer membrane ion channels.
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PMID:Mitochondrial voltage-dependent anion channel. Immunochemical and immunohistochemical characterization in rat brain. 822 52

The peripheral type benzodiazepine receptor (PBR) binds benzodiazepines such as RO5-4864 and isoquinoline carboxamide derivatives such as PK11195. This receptor includes an Mr 18,000 isoquinoline-binding subunit predominantly located in mitochondrial mem- branes. This protein has been found to copurify with two other mitochondrial proteins, namely the outer membrane voltage-dependent anion channel (VDAC), also known as mitochondrial porin, and the inner membrane adenine nucleotide carrier. In vitro reconstitution experiments suggested that the PBR was a multimeric complex in which the isoquinoline binding site was on the Mr 18,000 subunit, denoted pk18, whereas the benzodiazepine binding site required the association of this subunit with VDAC to be expressed. Untransformed cells of the yeast Saccharomyces cerevisiae are devoid of specific binding sites for isoquinolines and benzodiazepines, whereas yeast cells transformed with a pk18-expressing vector exhibit RO5-4864 and PK11195 binding sites that are pharmacologically identical to those of the PBR. To clarify the role of VDAC and of the adenine nucleotide carrier, if any, in the constitution of the benzodiazepine binding site, yeast host strains were constructed in which the corresponding genes had been knocked out. Mitochondria prepared from pk18-producing cells devoid of either VDAC or adenine nucleotide carrier exhibit both benzodiazepine and isoquinoline carboxamide binding sites with little or no change in the Kd values as compared with the wild-type background. These results rule out the contention that VDAC is indispensable for establishing the benzodiazepine binding site and are in agreement with the hypothesis that the Mr 18,000 subunit carries both the isoquinoline carboxamide and benzodiazepine binding domains.
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PMID:The Mr 18,000 subunit of the peripheral-type benzodiazepine receptor exhibits both benzodiazepine and isoquinoline carboxamide binding sites in the absence of the voltage-dependent anion channel or of the adenine nucleotide carrier. 934 65

Mitochondrial benzodiazepine receptor (mBzR) is a type of peripheral benzodiazepine receptor that is located in the outer membrane of mitochondria. It is an 18-kDa protein that can form a multimeric complex with voltage-dependent anion channel (32 kDa) and adenine nucleotide translocator (30 kDa). mBzR is found in various species and abundantly distributed in peripheral tissues, including the cardiovascular system. The mitochondria are well known as the site of energy production, and the heart is the organ that highly requires this energy supply. In the past decades, it has been shown that mBzR plays a critical role in regulating mitochondrial and heart functions. A growing body of evidence demonstrates that mBzR is associated with regulation of mitochondrial respiration, mitochondrial membrane potential, apoptosis, and reactive oxygen species production. Moreover, mBzR has been suggested to play a role in alteration of physiological effects in the heart such as contractility and heart rate. mBzR is involved in the pathologic condition such as ischemia/reperfusion injury, responses to stress, and changes in electrophysiological properties and arrhythmogenesis. In this review, evidence of the roles of mBzR in the heart under both physiological and pathologic conditions is presented. Clinical studies regarding the use of pharmacologic intervention involving mBzR in the heart are also discussed as a possible target for the treatment of electrical and mechanical dysfunction in the heart.
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PMID:Roles of mitochondrial benzodiazepine receptor in the heart. 2145 78