Disease relevance of Dbi

• We show here that the relatively high basal promoter activity of the rat ACBP gene in fibroblasts and hepatoma cells relies on sequences between -331 to -182 and on the Sp1 and NF-Y sites at -172 and -143, respectively [1].
• To test this hypothesis, mouse recombinant (mr) ACBP was engineered to contain the native mouse ACBP amino acid sequence expressed as a fusion protein at high levels (>150 mg/L) in Escherichia coli [2].
• Here, we show that deletion of Acbp in mouse results in sebocyte hyperplasia and sparse, matted hair with a greasy appearance [3].

Psychiatry related information on Dbi

• These data suggest a pivotal role for GABA-A and mitochondrial DBI receptors in the hyperphagic effects of neurosteroids and reinforces a role for endogenous neurosteroids in regulating feeding behavior [4].

High impact information on Dbi

• Thus endozepine, a ligand of the peripheral benzodiazepin receptor (whose occupation may facilitate mitochondrial membrane permeabilization), was found among the released proteins [5].
• Interestingly, the E prostanoid (EP) receptors EP2 and EP4 are elevated on donor-derived phagocytes post-BMT [6].
• Pulmonary fibroblasts from untreated mice expressed all four E prostanoid (EP) receptors for PGE(2) [7].
• By using PPARalpha expressed in Sf21 cells for electrophoretic mobility shift assays, we demonstrate that S-hexadecyl-CoA was able to increase the mobility of the PPARalpha-containing heterodimer even in the presence of a molar excess of acyl-CoA-binding protein, mimicking the conditions found in vivo [8].
• Furthermore, in the clones with the highest levels of ACBP antisense expression, the induction of expression of the adipogenic transcription factors peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha as well as several adipocyte-specific genes was significantly delayed and reduced [9].

Chemical compound and disease context of Dbi

• The present studies were undertaken to investigate the neuroactive steroidal modulation of feeding behavior and possible involvement of gamma-aminobutyric acid type-A (GABA-A) and mitochondrial diazepam binding inhibitor (DBI) receptors (MDR) in food-deprived male mice [4].

Biological context of Dbi

• The acyl-CoA binding protein (ACBP) is a 10 kD intracellular lipid binding protein that binds and transports acyl-CoA esters [1].
• PPARalpha and PPARgamma do not require sequences upstream of -182 for transactivation; however, SREBP-1c requires the synergistic action of sequences in intron 1 for transactivation of the ACBP promoter [1].
• The adipogenic potential of antisense-expressing cells was partially restored by transfection with a vector expressing high levels of ACBP [9].
• Purification and cleavage of the fusion tag resulted in mrACBP identical to native ACBP as shown by mass (10000.5 Da) and amino acid sequence (peptide mapping after proteolysis) determined by matrix-assisted laser desorption time of flight (MALDI-TOF) mass spectroscopy [2].
• Its moderate to high abundance, as judged from mRNA levels, in several organs suggests that DBI might have functions other than, or in addition to, the possible regulation of benzodiazepine binding sites [10].

Anatomical context of Dbi

• In addition, PPARalpha mediates the induction of ACBP expression in response to peroxisome proliferators [1].
• In hepatocytes, SREBP-1c is the main regulator of ACBP in response to changes in insulin levels during fasting/refeeding [1].
• Inhibition of 3T3-L1 adipocyte differentiation by expression of acyl-CoA-binding protein antisense RNA [9].
• Pools of 3T3-L1 cells transfected with vectors expressing ACBP antisense RNA showed significantly less lipid accumulation as compared with cells transfected with the control vector [9].
• Taken together, these data indicated for the first time that mrACBP interacted preferentially with anionic phospholipid-rich, highly curved membranes to facilitate transfer of ACBP-bound ligands [2].

Associations of Dbi with chemical compounds

• Fatty acids are activated to CoA esters, which bind with high affinity to the acyl-CoA-binding protein (ACBP) [11].
• Ethanol stimulates diazepam binding inhibitor (DBI) mRNA expression in primary cultured neurons [12].
• Its wide-spread distribution in non-neural tissues outside the brain suggests that DBI has various functions other than GABA-mediated neurotransmission [13].
• Since DBI is identical with the acyl-CoA binding protein, which has the ability to bind long chain acyl-CoA esters, the major function of DBI may possibly be related to lipid metabolism [13].
• Prostaglandin E(2) exerts its biological activity through binding to its membrane receptors, E-prostanoid (EP) receptors [14].

Physical interactions of Dbi

• Diazepam binding inhibitor (DBI) is a putative endogenous ligand capable of binding to the central type benzodiazepine (BZD) receptor located on the GABAA receptor and the peripheral type BZD receptor on the mitochondrial outer membrane [15].

Co-localisations of Dbi

• ACBP contains an endoplasmic reticulum retention motif and significantly colocalized with acyl-CoA cholesteryl acyltransferase 2 (ACAT2) and endoplasmic reticulum markers in L-cell fibroblasts and hepatoma cells, respectively [16].

Regulatory relationships of Dbi

• PPARalpha counteracts this effect by stimulating ACBP expression during fasting [1].
• NMDA receptor activation enhances diazepam binding inhibitor and its mRNA expressions in mouse cerebral cortical neurons [17].

Other interactions of Dbi

• We present evidence that endogenous ACBP, ALBP, and KLBP not only localize to the cytoplasm but also exhibit a prominent nuclear localization in 3T3-L1 adipocytes [11].
• In addition, forced expression of ACBP, ALBP, and KLBP in CV-1 cells resulted in a substantial accumulation of all three proteins in the nucleus [11].
• (v) Cytoplasmic LCFA-CoA binding proteins such as acyl-CoA binding protein, sterol carrier protein-2, and liver-FA binding protein slowed the process of 16:1-CoA degradation proportional to their respective affinities for this ligand [18].
• To resolve the role of fatty acyl CoA binding independent of cholesterol binding/transfer, a protein that exclusively binds fatty acyl CoA (acyl CoA binding protein, ACBP) was compared [16].
• These EtOH-induced increases in DBI mRNA expression were further elevated after the additional cultivation of neurons under EtOH-free condition. beta-Actin mRNA expression was not altered by similar EtOH treatments [12].

Analytical, diagnostic and therapeutic context of Dbi

• Reversed-phase HPLC indicated that DBI-like peptides were almost exclusively of the triakontatetraneuropeptide size [19].
• DBI-like peptides, investigated either by immunohistochemistry or by radioimmunoassay, were expressed to similar extents in mutant and control mice [19].
• The effect of nicotine on the expression of diazepam binding inhibitor (DBI) mRNA in primary cultured cerebral cortical neurons was examined using Northern blot analysis [20].
• Consistent with the previous findings, the in situ hybridization result showed very strong signals of DBI mRNA around the regions of the third ventricle, especially the lining cells, the arcuate nucleus of the hypothalamus and the cerebellum, in both socially isolated and group-housed animals [21].
• Unexpectedly, however, semi-quantitative experiments with reverse transcription polymerase chain reaction technique revealed that socially isolated mice had significantly less expression of DBI mRNA in the hypothalamus than group-housed animals, and no difference in the expression in the other brain areas was observed between two animal groups [21].

References