Disease relevance of DBI

• This sequence was engineered for expression in E. coli, and recombinant DBI exhibits identical biochemical and antigenic characteristics of natural human DBI [1].
• Moreover, the amount of DBI and its processing products was found to be increased in the CSF of patients with hepatic encephalopathy (HE) (Rothstein, McKhann, Guarneri, Barbaccia, Guidotti and Costa, 1989; Guarneri, Berkovich, Guidotti and Costa, 1990) [2].
• The high expression of DBI in brain tumors might play a role in the neoplastic growth of glial cells via the mitochondrial benzodiazepine receptor, or it may be involved in the regulation of the high energy consumption of these tumors via acyl-CoA metabolism [3].
• We have assayed the total cholesterol (TC) and the DBI plasma concentrations in patients with liver cirrhosis complicated by hepatocellular carcinoma (HCC) in comparison with those of uncomplicated liver cirrhosis [4].
• Androgen regulation of the messenger RNA encoding diazepam-binding inhibitor/acyl-CoA-binding protein in the human prostatic adenocarcinoma cell line LNCaP [5].

Psychiatry related information on DBI

• DBI can be postulated as a candidate gene for psychiatric phenotypes including anxiety, mood, and psychotic disorders [6].
• The measurement of DBI immunoreactivity (DBI-IR) in CSF of panic-disorder patients and normal controls was undertaken to assess whether there were differences in the CSF concentration of this peptide to assess possible relationships with other monoamines and peptides [7].
• CSF neuroactive steroids in affective disorders: pregnenolone, progesterone, and DBI [8].
• These lines of data suggest that cerebral DBI expression in brain may participates in formation of drug dependence and/or emergence of withdrawal syndrome [9].
• In patients with different types of dementia, the levels of CSF DBI were significantly increased in a group with normal pressure hydrocephalus [10].

High impact information on DBI

• Peripheral-type benzodiazepine/diazepam binding inhibitor receptor: biological role in steroidogenic cell function [11].
• Alcoholics with onset before and after 20 years of age also differed significantly from each other for cerebrospinal fluid concentrations of diazepam-binding inhibitor and somatostatin [12].
• This deviation was not accompanied by an increase in glial cell number (examined chemically by assay of diazepam-binding inhibitor immunoreactivity and microscopically by density of staining with the Holzer technique) [13].
• Diazepam-binding inhibitor is present, though not exclusively, in gamma-aminobutyric acid (GABA)-containing neurons where it is believed to inhibit GABAergic neurotransmission mediated by GABA by binding to the benzodiazepine-GABA receptor complex [14].
• Since an impairment of central GABAergic tone has been postulated to be associated with a number of neuropsychiatric disorders, we measured human diazepam-binding inhibitor immunoreactivity in the cerebrospinal fluid (CSF) of patients suffering from endogenous depression, schizophrenia, and dementia of the Alzheimer's type [14].

Chemical compound and disease context of DBI

• Diazepam binding inhibitor and total cholesterol plasma levels in cirrhosis and hepatocellular carcinoma [4].
• Cerebral DBI expression significantly increases in animals with drug dependence induced by these drugs, and in the cases of nicotine- and morphine-dependent mice concomitant administration of antagonists for nicotinic acetylcholine and opioid receptors, respectively, abolished the increase [9].
• Alimentary reactive hypoglycemia: effects of DBI and dilantin on insulin secretion [15].
• Peripheral benzodiazepine receptors were present in all the tumor types studied, whereas central benzodiazepine receptors and diazepam-binding inhibitor were detectable in astrocytomas and glioblastomas and undetectable in meningiomas, neurinomas, and metastases [16].
• Targeting Prostaglandin E EP Receptors to Inhibit Metastasis [17].

Biological context of DBI

• ACBP/DBI has previously been mapped to chromosome 2, although this was recently disputed, and a chromosome 6 location was suggested [18].
• To identify potential members of this gene family, degenerate oligonucleotides corresponding to highly conserved regions of ACBP/DBI were used to screen a human genomic DNA library using the polymerase chain reaction [18].
• The results of these experiments place ASSP1 sequences on human chromosome 6, IFNB3 on human chromosome 8, and DBI on human chromosome 6 [19].
• Molecular cloning and chromosomal localization of a pseudogene related to the human acyl-CoA binding protein/diazepam binding inhibitor [18].
• However, Southern blot analyses, in situ hybridizations, and somatic cell hybrid chromosomal mapping all suggest that there are multiple ACBP/DBI-related sequences in the genome [18].

Anatomical context of DBI

• DBI and TTN activate steroidogenesis by binding to a specific receptor located in the outer mitochondrial membrane, termed mitochondrial DBI receptor complex (MDRC) [20].
• The ACBP protein is consistently expressed in monocytes of all donors [21].
• The role of these sites and DBI in adrenal gland, testis, and kidney remains to be determined [1].
• Two different DBI transcripts capable of encoding polypeptides of 86 and 104 amino acids were detected in all the human tissues and cell lines studied [22].
• We conclude that DBI-derived peptides induce [Ca2+]i changes and modulate neutrophil function mainly through pBR-independent pathways [23].

Associations of DBI with chemical compounds

• MDRC is a hetero-oligomeric protein: only the subunit that includes the DBI and benzodiazepine (BZD) recognition sites has been cloned [20].
• In addition, DBI directly promotes loading of cholesterol to P450scc [24].
• As HTZ-19 cells respond in a dose-dependent manner to midozolam, DBI may interfere with growth regulation mediated by diazepam receptor sites [25].
• In these cells, DBI and some of its processing products bind to the mitochondrial DBI receptor (MDR), located on the outer mitochondrial membrane, and stimulate pregnenolone formation by facilitating cholesterol access to the inner mitochondrial membrane where the cytochrome P-450 side chain cleavage enzyme is located [26].
• Through this action, DBI indirectly modulates gamma-aminobutyric acid (GABA)-mediated inhibitory neurotransmission [6].

Regulatory relationships of DBI

• Interleukin-8 production induced by the endozepine triakontatetraneuropeptide in human neutrophils: role of calcium and pharmacological investigation of signal transduction pathways [27].

Other interactions of DBI

• DBIP1 bears extensive sequence homology to ACBP/DBI but lacks the introns predicted by rat and duck genomic sequence studies [18].
• New chromosomal mapping assignments for argininosuccinate synthetase pseudogene 1, interferon-beta 3 gene, and the diazepam binding inhibitor gene [19].
• Ex vivo-derived monocytes could be used in additional studies for analyzing differences in genotype-dependent expression levels of genes involved in fat assimilation such as ACBP, MACS1 or PPARgamma [21].
• In addition, CNBr cleavage and purification of resulting peptides revealed diazepam binding inhibitor (DBI, 8 kD) and melanoma inhibiting activity (MIA, 11 kD) [25].
• In CSF, the content of DBI changes in association with corticotropin releasing factor (CRF) (Roy, Pickar, Gold, Barbaccia, Guidotti, Costa and Linnoila, 1989) [2].

Analytical, diagnostic and therapeutic context of DBI

• Based on these data we propose a model where the interaction of DBI with PBR, at the outer/inner membrane contact sites, is the signal transducer of hormone-stimulated and constitutive steroidogenesis at the mitochondrial level [24].
• After 9 days from the hypophysectomy, the levels of DBI-like immunoreactivity (DBI-LI) and DBI-mRNA declined to approximately 20% of their normal value; in contrast MDR-density and MDR-mRNA levels were reduced by 50-60% and were associated to a similar decrease in the activity of type A monoamine oxidase, a marker for mitochondrial proteins [26].
• RT-PCR amplification showed that the mRNA encoding the endozepine precursor diazepam-binding inhibitor is expressed in the human testis [28].
• As demonstrated by Northern blot analysis, the mRNA encoding DBI/ACBP was expressed in prostate tissue and in the three human prostatic adenocarcinoma cell lines tested: LNCaP, PC-3 and DU-145 [5].
• One protein, which was decreased in concentration in both diseases, was characterised as diazepam binding inhibitor (DBI) by N-terminal sequence analysis [29].

References