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C Ferrarese - One of the best experts on this subject based on the ideXlab platform.
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reduced fasting plasma levels of Diazepam Binding Inhibitor in adolescents with anorexia nervosa
International Journal of Eating Disorders, 2013Co-Authors: E Conti, C Ferrarese, L Tremolizzo, M Bomba, Orlando Uccellini, Maria Sara Rossi, Maria Elisabetta Raggi, Francesca Neri, R NacinovichAbstract:Objective: Altered expression and/or function, both peripherally and centrally, of various neuropeptides is involved in the neurophysiology of anorexia nervosa (AN). Diazepam-Binding Inhibitor (DBI) is an interesting peptide for understanding this crosstalk. The aim of this work was to assess fasting plasma levels of DBI and leptin in patients with AN. Method: Twenty-four AN adolescents were recruited together with 10 agecomparable healthy controls. Neuropeptide determinations were performed on plasma samples by enzymelinked immunosorbent assays. Patients with AN were further characterized for the presence of a depressive state or anxiety by using, respectively, the Children’s Depression Inventory or the State-Trait Anxiety Inventory form Y. Results: Levels of both plasma DBI and leptin were reduced in patients with AN (40 and 70%, respectively). DBI levels displayed a tendency to increase in the presence of a depressive state, although not with anxiety, whereas leptin levels correlated exclusively with body mass index. Discussion: These data further extend our knowledge of neuropeptide dysfunction in AN, and plasma DBI may represent a marker for this disease, in particular considering its correlation with comorbid mood disorders.
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endogenous benzodiazepine like compounds and Diazepam Binding Inhibitor in serum of patients with liver cirrhosis with and without overt encephalopathy
Gut, 1998Co-Authors: R Avallone, I Venturini, Lorenzo Corsi, Maria Luisa Zeneroli, C Ferrarese, P Schreier, M Kleinschnitz, Franco Farina, Claudia Baraldi, N PecoraAbstract:Background/Aim—Despite some controversy, it has been suggested that endogenous benzodiazepine plays a role in the pathogenesis of hepatic encephalopathy. The aim of the present study was to evaluate the concentrations of endogenous benzodiazepines and the peptide, Diazepam Binding Inhibitor, in the blood of patients with liver cirrhosis with and without overt encephalopathy, and to compare these levels with those of consumers of commercial benzodiazepines. Subjects—Normal subjects (90), benzodiazepine consumers (14), and cirrhotic patients (113) were studied. Methods—Endogenous benzodiazepines were measured by the radioligand Binding technique after high performance liquid chromatography (HPLC) purification. The presence of Diazepam and N-desmethylDiazepam was assayed by HPLC-electrospray tandem mass spectrometry. Diazepam Binding Inhibitor was studied in serum by radioimmunoassay. Results—Endogenous benzodiazepines were below the limit of detection in 7% of patients with encephalopathy. When detectable, their levels were at least comparable with those of benzodiazepine consumers and correlated with the liver dysfunction but not the stage of encephalopathy. Serum levels of Diazepam Binding Inhibitor tended to decrease when endogenous benzodiazepines levels increased. Conclusions—Endogenous benzodiazepines may accumulate in patients with liver cirrhosis during the course of the disease, and the phenomenon appears to be independent of the presence or absence of encephalopathy. Keywords: benzodiazepine consumers; Diazepam Binding Inhibitor; endogenous benzodiazepines; liver cirrhosis; overt hepatic encephalopathy
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Diazepam Binding Inhibitor and total cholesterol plasma levels in cirrhosis and hepatocellular carcinoma
Regulatory Peptides, 1998Co-Authors: I Venturini, M Frigo, H Alho, Lorenzo Corsi, Maria Luisa Zeneroli, C Ferrarese, Franco Farina, Claudia Baraldi, N Pecora, M BaraldiAbstract:Abstract Cholesterol is used by cells for biosynthetic processes and for steroid synthesis. Although the role of cholesterol in tumorigenesis is not clear it is known that steroids are important factors in human carcinogenesis. A polypeptide, Diazepam Binding Inhibitor (DBI), which is an endogenous ligand for peripheral benzodiazepine receptors enhances steroidigenesis by promoting cholesterol delivery to the inner mitochondrial membrane which represents the rate-limiting step of steroid biosynthesis. 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. TC and DBI levels have been studied in 73 cirrhotic patients and in 23 patients with HCC. Both TC and DBI levels were higher in HCC patients when compared with age, sex and Child–Pugh class matched cirrhotic controls. The values (mean±S.D.) in patients in Child–Pugh class B and C with and without HCC were respectively 128±30 mg/dl vs. 106±27 mg/dl ( P P
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Diazepam Binding Inhibitor dbi in the plasma of pediatric and adult epileptic patients
Epilepsy Research, 1998Co-Authors: C Ferrarese, Tiziana Cogliati, Rachele Tortorella, Claudio Zucca, G Bogliun, Ettore Beghi, Davide Passoni, C Zoia, Barbara Begni, Larissa AiroldiAbstract:Abstract The polypeptide Diazepam Binding Inhibitor (DBI) displays epileptogenic activity by Binding to benzodiazepine receptors. We analyzed DBI concentrations in the plasma of pediatric and adult epileptic patients, as a possible peripheral marker in epilepsy. DBI plasma concentrations are significantly higher (+62%, P P P
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modifications of Diazepam Binding Inhibitor and peripheral benzodiazepine receptors in the lymphocytes of epileptic patients
Italian Journal of Neurological Sciences, 1996Co-Authors: C Ferrarese, M Frigo, N Pecora, C Marzorati, G Bianchi, M Perego, R Riva, G Moretti, L FrattolaAbstract:Recent experimental evidence has suggested that peripheral benzodiazepine receptors (PBR) may play a role in epilepsy and antiepileptic drug action. Since PBR are also present in circulating lymphocytes, and may interact with anticonvulsant drugs, this study was designed to look for possible modifications of these receptors and their endogenous ligand Diazepam Binding Inhibitor (DBI) in the lymphocytes of epileptic patients treated with various drugs. PBR levels were 50% to 80% higher in patients treated with carbamazepine, phenobarbital and valproic acid than in controls and untreated epileptics. DBI levels were significantly increased in the lymphocytes of untreated patients, and showed only a slight further increase after anticonvulsant therapy.
H Alho - One of the best experts on this subject based on the ideXlab platform.
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increased expression of peripheral benzodiazepine receptors and Diazepam Binding Inhibitor in human tumors sited in the liver
Life Sciences, 1999Co-Authors: I Venturini, H Alho, I Podkletnova, Lorenzo Corsi, Elena Rybnikova, Riccardo Pellicci, Mario Baraldi, Markku Peltohuikko, Pauli Helen, Maria Luisa ZeneroliAbstract:Abstract The peripheral benzodiazepine receptor system triggers intracellular metabolic events and has been associated with cell proliferation. Its endogenous ligand, the Diazepam Binding Inhibitor, contributes to steroidogenesis by promoting cholesterol delivery to the inner mitochondrial membrane. The present study was undertaken to verify whether this system is altered in tumors sited in the liver. Peripheral benzodiazepine receptors and Diazepam Binding Inhibitor were studied using immunocytochemistry and in situ hybridization in 9 human tumors sited in the liver, in liver hyperplasia, cirrhotic nodular regeneration, intestinal adenocarcinoma and in surrounding non-tumoral tissue. Immunocytochemical staining and in situ hybridization demonstrated that peripheral benzodiazepine receptors and Diazepam Binding Inhibitor were more prominently expressed in neoplastic cells than in non-tumoral tissue. They were present in the same cells, suggesting that Diazepam Binding Inhibitor may act in an intracrine manner in these cells. Higher peripheral benzodiazepine receptors and Diazepam Binding Inhibitor expression in tumor cells suggest an implication of this system in the metabolism of neoplastic cells. Furthermore the evaluation of peripheral benzodiazepine receptor and Diazepam Binding Inhibitor expression might be useful in evaluating malignancy and in diagnostic approaches of tumors in liver tissue.
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Diazepam Binding Inhibitor and total cholesterol plasma levels in cirrhosis and hepatocellular carcinoma
Regulatory Peptides, 1998Co-Authors: I Venturini, M Frigo, H Alho, Lorenzo Corsi, Maria Luisa Zeneroli, C Ferrarese, Franco Farina, Claudia Baraldi, N Pecora, M BaraldiAbstract:Abstract Cholesterol is used by cells for biosynthetic processes and for steroid synthesis. Although the role of cholesterol in tumorigenesis is not clear it is known that steroids are important factors in human carcinogenesis. A polypeptide, Diazepam Binding Inhibitor (DBI), which is an endogenous ligand for peripheral benzodiazepine receptors enhances steroidigenesis by promoting cholesterol delivery to the inner mitochondrial membrane which represents the rate-limiting step of steroid biosynthesis. 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. TC and DBI levels have been studied in 73 cirrhotic patients and in 23 patients with HCC. Both TC and DBI levels were higher in HCC patients when compared with age, sex and Child–Pugh class matched cirrhotic controls. The values (mean±S.D.) in patients in Child–Pugh class B and C with and without HCC were respectively 128±30 mg/dl vs. 106±27 mg/dl ( P P
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the transcriptional and translational control of Diazepam Binding Inhibitor expression in rat male germ line cells
DNA and Cell Biology, 1997Co-Authors: Meelis Kolmer, Markku Peltohuikko, Martti Parvinen, Christer Hoog, H AlhoAbstract:The Diazepam Binding Inhibitor [DBI, also known as acyl-CoA-Binding protein, (ACBP), or endozepine] is a 10-kD protein that has been suggested to be involved in the regulation of several biological processes such as acyl-CoA metabolism, steroidogenesis, insulin secretion, and γ-aminobutyric acid type A (GABAA)/benzodiazepine receptor modulation. DBI has been cloned from vertebrates, insects, plants, and yeasts. In mammals, DBI is expressed in almost all the tissues studied. Nevertheless, DBI expression is restricted to specific cell types. Here we have studied DBI gene expression in the germ-line cells of rat testis. The DBI gene was intensively transcribed in postmeiotic round spermatids from stages VI to VIII of the seminiferous epithelial cycle. A prominent, spermatid-specific upstream transcription initiation site was identified in addition to the multiple common transcriptional initiation sites found in the somatic tissues. However, no DBI protein was detected in round spermatids, suggesting that the...
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the characterization of two Diazepam Binding Inhibitor dbi transcripts in humans
Biochemical Journal, 1995Co-Authors: M Kolmer, A Rovio, H AlhoAbstract:We have investigated the expression of Diazepam Binding Inhibitor (DBI) (also called acyl-CoA-Binding protein or endozepine) transcripts in different human tissues and tissue culture cell lines by reverse-transcriptase assisted PCR and RNase protection assay. 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. The transcript coding for the 86 amino acid DBI polypeptide was found to represent the majority of the total DBI transcript pool.
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increased expression of Diazepam Binding Inhibitor in human brain tumors
Cell Growth & Differentiation, 1995Co-Authors: H Alho, M Kolmer, T Harjuntausta, Pauli HelenAbstract:Benzodiazepines, which are in extensive clinical use, can regulate neoplastic growth via benzodiazepine receptors. We have studied the expression of the Diazepam Binding Inhibitor (DBI) polypeptide, a putative endogenous ligand for benzodiazepine receptors in normal and pathological human brain. In normal brain, DBI immunoreactivity (IR) and mRNA were detected in all brain areas, with the highest levels in the cerebellum, amygdala, and hippocampus. In light and electron microscope immunohistochemistry, DBI-IR was only detected in glial and ependymal cells. In brain tumors, such as astrocytomas, glioblastomas and medulloblastomas, a much higher content of DBI-IR and -mRNA was found in normal tissues. The highest level of DBI expression was found in the most anaplastic tumors. DBI-IR was virtually undetectable in meningiomas and pituitary adenomas. 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.
Vassilios Papadopoulos - One of the best experts on this subject based on the ideXlab platform.
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role of the peripheral type benzodiazepine receptor and the polypeptide Diazepam Binding Inhibitor in steroidogenesis
The Journal of Steroid Biochemistry and Molecular Biology, 1995Co-Authors: Vassilios Papadopoulos, Shane A BrownAbstract:Steroidogenesis begins with the metabolism of cholesterol to pregnenolone by the inner mitochondrial membrane cytochrome P450 side-chain cleavage (P450scc) enzyme. The rate of steroid formation, however, depends on the rate of (i) cholesterol transport from intracellular stores to the inner mitochondrial membrane and (ii) loading of P450scc with cholesterol. We demonstrated that a key element in the regulation of cholesterol transport is the mitochondrial peripheral-type benzodiazepine receptor (PBR) and that the presence of the polypeptide Diazepam Binding Inhibitor (DBI) was vital for steroidogenesis. We also showed that DBI, as the endogenous PBR ligand, stimulates cholesterol transport. In addition, DBI directly promotes loading of cholesterol to P450scc. We review herein our studies on the structure, function, topography and hormonal regulation of PBR and DBI in steroidogenic cells. 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. Hormone-induced changes in PBR microenvironment/structure regulate the affinity of the receptor. PBR ligand Binding to a higher affinity receptor results in increased cholesterol transport. In addition, hormone-induced release (processing?) of a 30,000 MW DBI-immunoreactive protein from the inner mitochondrial membrane may result to the intramitochondrial production of DBI which directly stimulates loading of P450scc with cholesterol. Thus, in vivo, hormonal activation of these two mechanisms results in efficient cholesterol delivery and utilization and thus high levels of steroid synthesis.
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Diazepam Binding Inhibitor is a paracrine autocrine regulator of leydig cell proliferation and steroidogenesis action via peripheral type benzodiazepine receptor and independent mechanisms
Endocrinology, 1993Co-Authors: Martine Garnier, A S Brown, M Shoyab, Noureddine Boujrad, J Riond, P Ferrara, Carlos A Suarezquian, Vassilios PapadopoulosAbstract:Previous studies demonstrated that the polypeptide Diazepam Binding Inhibitor (DBI) and its receptor, the peripheral-type benzodiazepine receptor (PBR), are involved in the regulation of steroid biosynthesis and that one site of PBR action resides in mitochondria. In the present investigation, evidence is presented that a functional form of PBR is also present at the cell surface. First, PBR was immunolocalized in the rat testis using biotin-streptavidin peroxidase immunocytochemistry, and results revealed that PBR was present exclusively in the interstitial Leydig cells. Next, the distribution of PBR in MA-10 Leydig cells was further examined using confocal microscopy. MA-10 cells were either fixed and immunostained or fixed/permeabilized and immunostained for PBR, followed by generation of confocal microscope optical sections, three-dimensional reconstructions of these sections, and then generation of vertical confocal sections of the three-dimensional reconstruction. In the fixed/unpermeabilized cells,...
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endozepine Diazepam Binding Inhibitor in adrenocortical and leydig cell lines absence of hormonal regulation
Molecular and Cellular Endocrinology, 1992Co-Authors: A S Brown, Peter F Hall, M Shoyab, Vassilios PapadopoulosAbstract:Abstract One of the many effects which have been attributed to the peptide endozepine/Diazepam Binding Inhibitor (Ep/DBI) is the stimulation of adrenocortical and testicular Leydig cell mitochondrial steroidogenesis. We have used two cell lines (Y-1 mouse adrenal cell tumour and MA-10 mouse Leydig cell tumour), both of which exhibit hormone stimulated steroid production, to investigate the role of Ep/DBI in acute hormone stimulated steroidogenesis. The time course of incorporation of 35S-translabel into Ep/DBI and its turnover rate when the isotope was removed were examined. Cell samples were extracted and separated on Sep-Pak C18 columns and analysed using sodium dodecyl sulphate-poly-acrylamide gel electrophoresis (SDS-PAGE) and immunoblot analysis followed by fluorography as well as by direct scintillation counting. This allowed us to estimate the in vivo half-life of Ep/DBI and also to investigate the hormonal dependence of the peptide. Data presented here suggest that (i) Ep/DBI levels are not regulated by trophic hormones in these steroidogenic cell lines, and (ii) that the peptide has a relatively long half-life (> 3 h), a finding incompatible with suggestions of it having a rapid turnover. Therefore, it seems unlikely that control of Ep/DBI steroidogenic effects is via hormonal modulation of the peptide levels.
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Endozepine/Diazepam Binding Inhibitor in adrenocortical and Leydig cell lines: Absence of hormonal regulation
Molecular and Cellular Endocrinology, 1992Co-Authors: A S Brown, Peter F Hall, M Shoyab, Vassilios PapadopoulosAbstract:Abstract One of the many effects which have been attributed to the peptide endozepine/Diazepam Binding Inhibitor (Ep/DBI) is the stimulation of adrenocortical and testicular Leydig cell mitochondrial steroidogenesis. We have used two cell lines (Y-1 mouse adrenal cell tumour and MA-10 mouse Leydig cell tumour), both of which exhibit hormone stimulated steroid production, to investigate the role of Ep/DBI in acute hormone stimulated steroidogenesis. The time course of incorporation of 35S-translabel into Ep/DBI and its turnover rate when the isotope was removed were examined. Cell samples were extracted and separated on Sep-Pak C18 columns and analysed using sodium dodecyl sulphate-poly-acrylamide gel electrophoresis (SDS-PAGE) and immunoblot analysis followed by fluorography as well as by direct scintillation counting. This allowed us to estimate the in vivo half-life of Ep/DBI and also to investigate the hormonal dependence of the peptide. Data presented here suggest that (i) Ep/DBI levels are not regulated by trophic hormones in these steroidogenic cell lines, and (ii) that the peptide has a relatively long half-life (> 3 h), a finding incompatible with suggestions of it having a rapid turnover. Therefore, it seems unlikely that control of Ep/DBI steroidogenic effects is via hormonal modulation of the peptide levels.
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Diazepam Binding Inhibitor and its processing products stimulate mitochondrial steroid biosynthesis via an interaction with mitochondrial benzodiazepine receptors
Endocrinology, 1991Co-Authors: Vassilios Papadopoulos, E Costa, A. Berkovich, Karl E Krueger, Alessandro GuidottiAbstract:A recognition site for benzodiazepines structurally different from that linked to various γ-aminobutyric acid A (GABAA) receptor subtypes is located on the outer mitochondrial membranes of steroidogenic cells. This protein has been signified to be important in the regulation of steroid biosynthesis. Because of its location it is designated herein as the mitochondrial benzodiazepine receptor (MBR). A putative endogenous ligand for MBR is the peptide Diazepam Binding Inhibitor (DBI), previously shown to displace drugs from MBR and to be expressed and stored in steroidogenic cells rich in MBR. The two model systems used to study steroidogenic regulation by DBI were the Y-l adrenocortical and MA-10 Leydig cell lines previously shown to be applicable in studies of mitochondrial steroidogenesis. Both cell lines contain DBI as well as DBI processing products, including the DBI fragments that on reverse phase HPLC coelute with the naturally occurring triakontatetraneuropeptide [TTN; DBI-(17–50)] and octadecaneuro...
Alessandro Guidotti - One of the best experts on this subject based on the ideXlab platform.
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CSF levels of Diazepam-Binding Inhibitor correlate with REM latency in schizophrenia, a pilot study
European Archives of Psychiatry and Clinical Neuroscience, 1994Co-Authors: Daniel P. Van Kammen, Alessandro Guidotti, Mary E. Kelley, John A. Gurklis, Mark W. Gilbertson, Jeffrey L. Peters, Thomas C. Neylan, Patrizia Guaneri, Erminio CostaAbstract:CSF Diazepam-Binding Inhibitor-like immuno-reactivity (DBI-LI) and polysomnography were studied in 28 drug-free male schizophrenic (DSM-III-R) patients. They underwent a three-night polysomnography evaluation and a lumbar puncture. CSF DBI-LI correlated positively with REM latency, the REM latency/2d nonREM period ratio and stage-4% sleep, and negatively with stage-1% sleep. CSF DBI-LI did not correlate significantly with duration of sleep or sleep latency. CSF DBI-LI during haloperidol treatment did not correlate significantly with sleep EEG measures. The results of this first study of the relationship between endogenous DBI and sleep in humans suggest that physiological effects of DBI other than interactions with the BZD/GABAA receptor complex may explain its positive effects on sleep. However, the absence of similar sleep data in normal subjects precludes us from establishing a specific relationship between DBI and sleep in schizophrenia.
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mitochondrial Diazepam Binding Inhibitor receptor complex agonists antagonize dizocilpine amnesia putative role for allopregnanolone
Journal of Pharmacology and Experimental Therapeutics, 1994Co-Authors: Elena Romeo, E Costa, D L Cheney, I Zivkovic, Alessandro GuidottiAbstract:In rats trained to retain a passive avoidance response or to retrieve a learned task in the radial and water maze tests, a pretreatment with 2-hexyl-3-indoleacetamide (FGIN-1-27) (IC50 57 mumol/kg p.o.) or 4' chloroDiazepam (4'CD) (15 mumol/kg i.p.), two steroidogenic ligands at the mitochondria Diazepam-Binding Inhibitor receptor complex (MDRC), antagonized the performance deficit elicited by dizocilpine (0.3 mumol/kg i.p.), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. The 1-(2-chlorophenyl)-N-methyl-N-(-1-methyl-propyl)-3-isoquinoline carboxamide (PK-11195), an antagonist at MDRC in vivo, failed to modify the disruptive effect of dizocilpine in the passive avoidance response but reversed the FGIN-1-27- or 4' CD-induced antagonism of dizocilpine behavioral actions. Pretreatment with pregnenolone sulfate (48 mumol/kg i.p.), 3 alpha, 21-dihydroxy-5 alpha-pregnan-20-one (THDOC) (15 mumol/kg i.v.) and 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) (15 mumol/kg i.v.) also reduced the passive avoidance retention deficit elicited by dizocilpine. The (17-beta)-17-[[bis(1-methylethyl)amino[carbonyl]androstane-3,5-diene-3- carboxylic acid (SKF-105111), a 5 alpha-reductase Inhibitor, blocked the antagonism of dizocilpine behavioral actions by pregnenolone sulfate or by FGIN-1-27 but not those caused by THDOC or allopregnanolone either in normal or adrenalectomized-castrated rats. Thus, it is inferred that the amnesic effect of dizocilpine is counteracted by FGIN-1-27, 4'CD and pregnenolone sulfate because of their ability to increase brain accumulation of allopregnanolone.
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CSF Diazepam Binding Inhibitor and schizophrenia: Clinical and biochemical relationships
Biological Psychiatry, 1993Co-Authors: Daniel P. Van Kammen, Alessandro Guidotti, Mary E. Kelley, John A. Gurklis, Patrizia Guarneri, Mark W. Gilbertson, Jeffrey L. Peters, Erminio CostaAbstract:Abstract Diazepam-Binding Inhibitor (DBI) is a 9-kD neuropeptide that interacts with the benzodiazepine (BZD) Binding sites of the neuronal γ-aminobutyric acid type A (GABAA) receptor and with the glial mitochondrial BZD receptor (MBR). We explored the involvement of CSF DBI-LI in schizophrenia, based on the potential role of GABA in the negative symptoms associated with schizophrenia, the relationship of its receptors with dopamine and norepinephrine release, an and the proposed therapeutic efficacy of BZDs in schizophrenia. Clinical data, CSF DBI-LI and CSF monoamine measures were obtained in 65 drug-free male chronic (DSM-IIIR) schizophrenic patients, 53 of whom were also tested prior to haloperidol withdrawal. Following haloperidol withdrawal, CSF DBI-LI increased significantly. Drug-free CSF DBI-LI did not correlate with CSF monoamines. CSF DBI-LI was significantly higher in paranoid compared to chronic undifferentiated schizophrenic patients. The data suggest that DBI may have a symptom modulatory rather than an etiological role in schizophrenia.
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Diazepam Binding Inhibitor and its processing products stimulate mitochondrial steroid biosynthesis via an interaction with mitochondrial benzodiazepine receptors
Endocrinology, 1991Co-Authors: Vassilios Papadopoulos, E Costa, A. Berkovich, Karl E Krueger, Alessandro GuidottiAbstract:A recognition site for benzodiazepines structurally different from that linked to various γ-aminobutyric acid A (GABAA) receptor subtypes is located on the outer mitochondrial membranes of steroidogenic cells. This protein has been signified to be important in the regulation of steroid biosynthesis. Because of its location it is designated herein as the mitochondrial benzodiazepine receptor (MBR). A putative endogenous ligand for MBR is the peptide Diazepam Binding Inhibitor (DBI), previously shown to displace drugs from MBR and to be expressed and stored in steroidogenic cells rich in MBR. The two model systems used to study steroidogenic regulation by DBI were the Y-l adrenocortical and MA-10 Leydig cell lines previously shown to be applicable in studies of mitochondrial steroidogenesis. Both cell lines contain DBI as well as DBI processing products, including the DBI fragments that on reverse phase HPLC coelute with the naturally occurring triakontatetraneuropeptide [TTN; DBI-(17–50)] and octadecaneuro...
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Regulation of Diazepam Binding Inhibitor in Rat Adrenal Gland by Adrenocorticotropin
Endocrinology, 1991Co-Authors: M. Massotti, E. Slobodyansky, Erminio Costa, D. Konkel, Alessandro GuidottiAbstract:Diazepam Binding Inhibitor (DBI) is a 9-kDa polypeptide that was initially isolated from rat brain and subsequently found to be present in several peripheral tissues. DBI is particularly abundant in steroidogenic tissues, such as the adrenal glands and testes, which also contain a high concentration of peripheral/mitochondrial benzodiazepine receptors (MBRs). Because occupancy of adrenal MBRs with DBI results in increased steroidogenesis, we have investigated the relation between ACTH, DBI, and the MBR in the rat adrenal glands. Evidence presented here indicates that both the amount of DBI and its rate of synthesis in the adrenal cortex are under the control of ACTH. Seven and 9 days after hypophysectomy, the amount of DBI-like immunoreactivity (DBI-LI) in rat adrenal glands decreased dramatically from approximately 80 to 15 ng/mg tissue. The administration of single dose of ACTH (ACTH residues 1–39; 200 mU/kg, iv) or repeated doses of ACTH-R (ACTH in saline containing 16% gelatin; 15 U/kg, sc, twice dail...
Hubert Vaudry - One of the best experts on this subject based on the ideXlab platform.
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acute food deprivation reduces expression of Diazepam Binding Inhibitor the precursor of the anorexigenic octadecaneuropeptide odn in mouse glial cells
Journal of Molecular Endocrinology, 2010Co-Authors: Vincent Compere, Hubert Vaudry, Georges Pelletier, Damien Lanfray, Helene Castel, Fabrice Morin, Jerome Leprince, B Dureuil, Marie-christine TononAbstract:In the central nervous system of mammals, the gene encoding Diazepam-Binding Inhibitor (DBI) is exclusively expressed in glial cells. Previous studies have shown that central administration of a DBI processing product, the octadecaneuropeptide ODN, causes a marked inhibition of food consumption in rodents. Paradoxically, however, the effect of food restriction on DBI gene expression has never been investigated. Here, we show that in mice, acute fasting dramatically reduces DBI mRNA levels in the hypothalamus and the ependyma bordering the third and lateral ventricles. I.p. injection of insulin, but not of leptin, selectively stimulated DBI expression in the lateral ventricle area. These data support the notion that glial cells, through the production of endozepines, may relay peripheral signals to neurons involved in the central regulation of energy homeostasis.
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localization of Diazepam Binding Inhibitor and peripheral type benzodiazepine Binding sites in the rat ovary
Anatomy and Embryology, 1994Co-Authors: D Toranzo, Hubert Vaudry, Marie-christine Tonon, Yiai Tong, Georges PelletierAbstract:Diazepam-Binding Inhibitor (DBI) is the precursor of a family of peptides, including an octadecaneuropeptide (ODN), that share with DBI the ability to specifically displace benzodiazepines (BZD) from their receptors. An association of ODN with the peripheral type BZD receptors (PBR) has been reported in the brain and a few peripheral tissues. In order to investigate whether DBI and PBR are present in ovarian tissue, we have localized DBI by means of immunocytochemistry, in situ hybridization and autoradiography of PBR in the rat ovary. Immunocytochemical localization was achieved by means of rabbit antibodies developed against rat ODN. Immunostaining was located in the cytoplasm of the theca interna, corpus luteum and interstitial gland cells, but not in the granulosa cells. Hybridization signal obtained following in situ hybridization with a [35S1]-labelled single-stranded RNA probe complementary to DBI mRNA was observed in all the steroid-secreting cells, including granulosa cells of developing and mature follicles. Autoradiographic localization of PBR obtained by incubating ovary sections with [3H] PK11195, a ligand selective for PBR, revealed the presence of specific labelling in all the steroid-secreting cells. These results, which demonstrate for the first time that the ovarian steroid-secreting cells contain both PBR and its endogenous ligand, suggest that the BZD receptor might be involved in the regulation of ovarian function.
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frog Diazepam Binding Inhibitor peptide sequence cdna cloning and expression in the brain
Proceedings of the National Academy of Sciences of the United States of America, 1994Co-Authors: Isabelle Lihrmann, J. Michael Conlon, Marie-christine Tonon, Hervé Tostivint, Rianne Raijmakers, Jean-christophe Plaquevent, Hubert VaudryAbstract:Abstract Three peptides derived from Diazepam-Binding Inhibitor (DBI) were isolated in pure form from the brain of the frog Rana ridibunda. The primary structures of these peptides showed that they correspond to mammalian DBI-(1-39), DBI-(58-87), and DBI-(70-87). A set of degenerate primers, whose design was based on the amino acid sequence data, was used to screen a frog brain cDNA library. The cloned cDNA encodes an 87-amino acid polypeptide, which exhibits 68% similarity with porcine and bovine DBI. Frog DBI contains two paired basic amino acids (Lys-Lys) at positions 14-15 and 62-63 and a single cysteine within the biologically active region of the molecule. Northern blot analysis showed that DBI mRNA is expressed at a high level in the brain but is virtually absent in peripheral tissues. The distribution of DBI mRNA and DBI-like immunoreactivity in the frog brain was studied by in situ hybridization and immunocytochemistry. Both approaches revealed that the DBI gene is expressed in ependymal cells and circumventricular organs lining the ventricular cavity. Since amphibia diverged from mammals at least 250 million years ago, the data show that evolutionary pressure has acted to conserve the structure of DBI in the vertebrate phylum. The distribution of both DBI mRNA and DBI-like immunoreactivity indicates that DBI is selectively expressed in glial cells.
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Peptide Sequence and Molecular Cloning of Frog Diazepam-Binding Inhibitor
Netherlands Journal of Zoology, 1994Co-Authors: Hubert Vaudry, J. Michael Conlon, Marie-christine Tonon, Hervé Tostivint, Rianne Raijmakers, Jean-christophe Plaquevent, Isabelle LihrmannAbstract:Three peptides derived from Diazepam-Binding Inhibitor (DBI), an endogenous ligand for the benzodiazcpine receptor, were isolated from an extract of frog brain and their primary structures were determined. On the basis of the amino acid sequence data, a cDNA encoding frog DBI was isolated from a whole brain cDNA library. This cDNA was used to study DBI gene expression in various frog tissues by Northern blot analysis, RT-PCR and in situ hybridization.
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ontogeny of Diazepam Binding Inhibitor related peptides endozepines in the rat brain
Neuroscience, 1993Co-Authors: Hubert Vaudry, Maria M Malagon, F J C Van Strien, Georges Pelletier, Francisco Gracianavarro, Marie-christine TononAbstract:Abstract Benzodiazepine receptors are expressed very early in the brain during embryonic life, suggesting that endogenous ligands for these receptors may play an important role during ontogenesis in the central nervous system. In the present study, the distribution and characterization of Diazepam-Binding Inhibitor-related peptides (endozepines) in the rat brain was investigated during embryonic and postnatal development using an antibody raised against the biologically active region of the precursor molecule. Immunohistochemical labelling showed that, in newborn rats, endozepine-like immunoreactivity was present in ependymal cells of the hypothalamus. Although the number of positive cells increased by day 5, the intensity of the immunoreaction in each cell diminished. In 15-day-old rats, both the number of endozepine positive cells and the intensity of the immunoreaction increased in the ependymal layer. At day 40, a dense accumulation of immunoreactive tanycytes and glial cells was observed in the median eminence and the arcuate nucleus. Endozepines were detected by radioimmunoassay in all regions of the brain as early as embryonic day 18. The concentration of endozepine-related peptides increased in the hypothalamus and olfactory bulb during late gestation. Between birth and postnatal day 5, the levels of endozepines decreased two- to four-fold in all brain regions studied. Thereafter, endozepine concentration increased gradually until day 25. Reversed-phase high-performance liquid chromatography analysis of tissue extracts revealed that the olfactory bulb, pituitary, hypothalamus and cerebellum contained only one immunoreactive peak eluting at 39 min (peak C). In the telencephalon two peaks were observed: peak C and a second one eluting at 34 min (peak B). Peak B was present as early as embryonic day 20 and the ratio peak B/peak C gradually increased until day 25. At day 25 peak B was also detected in hippocampus, medulla oblongata, cortex and striatum extracts. In any brain region, no immunoreactivity co-eluting with the octadecaneuropeptide was observed. Sephadex G-50 gel filtration of hypothalamus extracts of 25-day-old animals, confirmed the existence of only one immunoreactive compound with an apparent molecular weight of 10,000. In the telencephalon two major species were resolved, with apparent molecular weights of 10,000 and 8800, and a minor one of 6500 mol. wt. In conclusion, the present study shows that endozepines are expressed in the rat brain as early as embryonic day 18 and the amount of endozepine-like material increases rapidly during the two days preceding birth. The results also indicate that Diazepam-Binding Inhibitor is processed to different molecular forms depending on the brain region. Taken together these data support the concept that endozepines may play important functions during brain development.