Disease relevance of BRD1

• Intracoronary thrombolysis with an acylated streptokinase-plasminogen activator (BRL 26921) in patients with acute myocardial infarction [1].
• Although the precise mechanism of action of BRL 49653 on PI3-Kinase activity is not completely clear, these findings improve our understanding of the insulin-sensitizing effects of the thiazolidinediones, possible drugs for the treatment of Type II (non-insulin-dependent) diabetes mellitus [2].
• A bromodomain-containing protein from tomato specifically binds potato spindle tuber viroid RNA in vitro and in vivo [3].
• BRL 42715 is a novel, highly potent beta-lactamase inhibitor with good activity against a broad range of beta-lactamases, including the class I enzymes of Enterobacter and Citrobacter spp [4].
• Compared with four beta-lactam antibiotics and amikacin, BRL 36650 and BMY-28142 were the most active against 509 Enterobacteriaceae, including cefotaxime-resistant isolates and resistant laboratory mutants [5].

Psychiatry related information on BRD1

• Evidence implicating BRD1 with brain development and susceptibility to both schizophrenia and bipolar affective disorder [6].
• The effects of BRL 46470A, a novel 5-HT3 receptor antagonist, and lorazepam on psychometric performance and the EEG [7].
• It is concluded that since the published animal data show that BRL 20627 has only weak dopamine antagonistic properties this study further implicates dopamine receptor blockade in the akathisia but not in the gastric effect of metoclopramide [8].
• Paired comparisons revealed no significant effect on Bmax of 6 weeks' treatment with imipramine, maprotiline, or BRL 14342 or of a course of electroconvulsive therapy [9].

High impact information on BRD1

• Reconstitution of recombinant nucleosomes bearing mutations in these lysine residues revealed the cascade of gene activation via a point-by-point interpretation of the histone code through the ordered recruitment of bromodomain-containing transcription complexes [10].
• The E2-interacting domain at the extreme C terminus and the chromatin targeting activity of a bromodomain-containing region are both essential for the corepressor activity of Brd4 [11].
• Using fluorescence resonance energy transfer, we show that bromodomain-containing proteins recognize different patterns of acetylated histones in intact nuclei of living cells [12].
• In the hepatocyte cell line AML-12, fenofibric acid, but not BRL 49653, induced LPL mRNA, whereas in 3T3-L1 preadipocytes, the PPARgamma ligand induced LPL mRNA levels much quicker and to a higher extent than fenofibric acid [13].
• Human gastric carcinoma cell line STKM-1 secretes a large protein that induces scattering of a rat liver epithelial cell line (BRL) into disconnected individual cells in monolayer culture [14].

Chemical compound and disease context of BRD1

• The ability of isoproterenol, glucagon, PGE1 and cholera toxin to stimulate the synthesis of cAMP and protein kinase activity in line of liver cells (BRL) and a line of rat hepatoma cells (H35) has been determined [15].
• Against Pseudomonas aeruginosa and other Pseudomonas species, BRL 36650 was more active than piperacillin, cefoperazone, and aztreonam and compared favorably with ceftazidime [16].
• Clinical isolates of Enterobacter species and P. aeruginosa which showed markedly reduced susceptibility to cefotaxime, ceftazidime, and aztreonam were only slightly less susceptible to BRL 36650 [16].
• Studies were performed to determine the effects of BRL 42715, a potent beta-lactamase inhibitor, on the activity of cefazolin and piperacillin against experimental intraperitoneal infections caused by either Escherichia coli or Serratia marcescens in rats [17].
• Among these 412 strains were 73 Citrobacter and Enterobacter strains, and 1 microgram of BRL 42715 per ml reduced the MIC50 of amoxicillin from greater than 128 to 2 micrograms/ml for the 48 cefotaxime-susceptible strains and from greater than 128 to 8 micrograms/ml for the 25 cefotaxime-resistant strains [18].

Biological context of BRD1

• A specific BRD1 2-marker 'risk' haplotype showed a frequency of approximately 10% in the combined case group versus approximately 1% in controls (P-value 2.8 x 10(-7)) [6].
• BRL maps to chromosome 22q13 and shows high levels of expression in testis and several cell lines [19].
• Proteins specific to the human NuA4 complexes include ruvB-like helicases and a bromodomain-containing subunit linked to ligand-dependent transcription activation by the thyroid hormone receptor [20].
• The PPARgamma ligand BRL 49653 and 15S-HETE caused a dose-dependent inhibition of PC3 proliferation in a 14-day soft agar colony-forming assay (IC50 of 3 and 30 microM, respectively) [21].
• In PC3 cells transiently transfected with a luciferase reporter linked to a PPAR response element, 1 microM BRL 49653 and 10 microM 15S-HETE caused approximately threefold and greater than twofold induction of PPAR-dependent transcription, respectively [21].

Anatomical context of BRD1

• Expression analysis of BRD1 mRNA revealed widespread expression in mammalian brain tissue, which was substantiated by immunohistochemical detection of BRD1 protein in the nucleus, perikaryal cytosol and proximal dendrites of the neurons in the adult rat, rabbit and human CNS [6].
• A monoclonal antibody raised to a BRL peptide sequence confirmed its widespread expression as a 120 Kd protein and demonstrated localization to the nucleus within spermatocytes [19].
• By quantitative real-time reverse transcription-PCR and Northern analysis, 3-day treatment with BRL 49653 and 15S-HETE caused a reduction of PPARgamma expression but a marked up-regulation of the PPAR response element containing adipocyte type fatty acid binding protein [21].
• Other monocyte markers, including OK M1, Co Mo2, BRL Mo1, BRL Mo2, and Leu M3 were consistently negative in both types of cells [22].
• This in vitro study compared the direct vasodilator effects of troglitazone and BRL 49653 in small arteries (n = 44) from human subcutaneous fat [23].

Associations of BRD1 with chemical compounds

• Neither inhibitors of ATP-sensitive K+ channels (BRL 31660 or glibenclamide, both at 10 microM) nor an inhibitor of small conductance Ca(2+)-activated K+ channels (apamin; 0.1 microM) were effective [24].
• Furthermore, we suppressed the oxidative burst by using the PPARgamma agonists 15-deoxy-Delta12,14-prostaglandin J2, BRL 49653, or ciglitazone [25].
• The thiazolidinediones troglitazone and BRL 49653 improve insulin sensitivity in humans and animals with insulin resistance [26].
• Differential vasoactive effects of the insulin sensitizers rosiglitazone (BRL 49653) and troglitazone on human small arteries in vitro [23].
• It is suggested that the antidiabetic and thermogenic properties of BRL 26830 are linked and that blood glucose acts either directly or indirectly as a substrate for thermogenesis [27].

Other interactions of BRD1

• The cloning, mapping and expression of a novel gene, BRL, related to the AF10 leukaemia gene [19].
• DNA sequencing of this clone and predicted amino acids showed more than 93% homology to RING3 kinase, a member of a newly described family of bromodomain-containing proteins that transactivates in the nucleus the promoters of a number of the E2F family of transcription factors [28].
• Acetylation-dependent chromatin reorganization by BRDT, a testis-specific bromodomain-containing protein [29].
• The chromosome 19 translocation breakpoint targets the BRD4 double bromodomain-containing gene, which functions in regulation of cell cycle progression [30].
• Using yeast two-hybrid screening, we identified a novel chromatin-associated bromodomain-containing protein, BRD7, as an E1B-AP5 interaction partner [31].

Analytical, diagnostic and therapeutic context of BRD1

• Improved glycemic control in C57Bl/KsJ (db/db) mice after treatment with the thermogenic beta-adrenoceptor agonist, BRL 26830 [27].
• When exposed to BRL 49653 for 5 days, preadipocytes from the human perirenal depot accumulated lipid, and a proportion of cells showed clear mitochondrial staining for UCP-1 protein by confocal microscopy [32].
• Reperfusion time in those patients treated with BRL 26921 alone amounted to 42 +/- 37 minutes [1].
• Vehicle or BRL 52537 treatment with continuous intravenous infusion was instituted at the onset of reperfusion and continued for 22 h [33].
• The 5-HT3 antagonist, BRL 46470 does not attenuate m-chlorophenylpiperazine (mCPP)-induced changes in human volunteers [34].

References