References of "Biochimica et biophysica acta"
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See detailImpact of BRAF kinase inhibitors on the miRNomes and transcriptomes of melanoma cells
Kreis, Stephanie UL; Kozar, Ines UL; Cesi, Giulia UL et al

in Biochimica et Biophysica Acta (2017)

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See detailTargeting histone lysine demethylases - progress, challenges, and the future.
Thinnes, Cyrille UL; England, Katherine S.; Kawamura, Akane et al

in Biochimica et biophysica acta (2014), 1839(12), 1416-32

N-Methylation of lysine and arginine residues has emerged as a major mechanism of transcriptional regulation in eukaryotes. In humans, N(epsilon)-methyllysine residue demethylation is catalysed by two ... [more ▼]

N-Methylation of lysine and arginine residues has emerged as a major mechanism of transcriptional regulation in eukaryotes. In humans, N(epsilon)-methyllysine residue demethylation is catalysed by two distinct subfamilies of demethylases (KDMs), the flavin-dependent KDM1 subfamily and the 2-oxoglutarate- (2OG) dependent JmjC subfamily, which both employ oxidative mechanisms. Modulation of histone methylation status is proposed to be important in epigenetic regulation and has substantial medicinal potential for the treatment of diseases including cancer and genetic disorders. This article provides an introduction to the enzymology of the KDMs and the therapeutic possibilities and challenges associated with targeting them, followed by a review of reported KDM inhibitors and their mechanisms of action from kinetic and structural perspectives. [less ▲]

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See detailTHAP1, the gene mutated in DYT6 dystonia, autoregulates its own expression.
Erogullari, Alev; Hollstein, Ronja; Seibler, Philip et al

in Biochimica et biophysica acta (2014), 1839(11), 1196-204

THAP1 encodes a transcription factor but its regulation is largely elusive. TOR1A was shown to be repressed by THAP1 in vitro. Notably, mutations in both of these genes lead to dystonia (DYT6 or DYT1 ... [more ▼]

THAP1 encodes a transcription factor but its regulation is largely elusive. TOR1A was shown to be repressed by THAP1 in vitro. Notably, mutations in both of these genes lead to dystonia (DYT6 or DYT1). Surprisingly, expressional changes of TOR1A in THAP1 mutation carriers have not been detected indicating additional levels of regulation. Here, we investigated whether THAP1 is able to autoregulate its own expression. Using in-silico prediction, luciferase reporter gene assays, and (quantitative) chromatin immunoprecipitation (ChIP), we defined the THAP1 minimal promoter to a 480bp-fragment and demonstrated specific binding of THAP1 to this region which resulted in repression of the THAP1 promoter. This autoregulation was disturbed by different DYT6-causing mutations. Two mutants (Ser6Phe, Arg13His) were shown to be less stable than wildtype THAP1 adding to the effect of reduced binding to the THAP1 promoter. Overexpressed THAP1 is preferably degraded through the proteasome. Notably, endogenous THAP1 expression was significantly reduced in cells overexpressing wildtype THAP1 as demonstrated by quantitative PCR. In contrast, higher THAP1 levels were detected in induced pluripotent stem cell (iPS)-derived neurons from THAP1 mutation carriers. Thus, we identified a feedback-loop in the regulation of THAP1 expression and demonstrated that mutant THAP1 leads to higher THAP1 expression levels. This compensatory autoregulation may contribute to the mean age at onset in the late teen years or even reduced penetrance in some THAP1 mutation carriers. [less ▲]

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See detailLocal signals with global impacts and clinical implications: lessons from the plasma membrane calcium pump (PMCA4).
Oceandy, Delvac; Mohamed, Tamer M. A.; Cartwright, Elizabeth J. et al

in Biochimica et biophysica acta (2011), 1813(5), 974-8

Calcium has been unequivocally regarded as a key signal messenger in almost every cell type. Calcium regulates a number of important cellular functions including cell growth, myofilament contraction, cell ... [more ▼]

Calcium has been unequivocally regarded as a key signal messenger in almost every cell type. Calcium regulates a number of important cellular functions including cell growth, myofilament contraction, cell survival and apoptosis as well as gene transcription. A complex regulatory mechanism of cellular calcium is needed to fine tune the precise calcium concentration in each subcellular location and also to transmit the signals carried by the calcium pool to the correct end target. In this article we will review the recently emerging role of the plasma membrane calcium/calmodulin dependent ATPase isoform 4 (PMCA4) in regulating calcium signalling. We will then focus on the function of this molecule in cardiomyocytes, in which PMCA4 forms protein-protein interactions with several key signalling molecules. Recent evidence has shown in vivo physiological functionalities and possible clinical implications of the PMCA4 signalling complex. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. [less ▲]

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See detailThe histone deacetylase inhibitor trichostatin A mediates upregulation of 5-lipoxygenase promoter activity by recruitment of Sp1 to distinct GC-boxes
Schnur, N.; Seuter, Sabine UL; Katryniok, C. et al

in Biochimica et Biophysica Acta (2007), 1771(10), 1271-1282

The histone deacetylase inhibitor trichostatin A (TsA) potently induces 5-lipoxygenase (5-LO) promoter activity in reporter gene assays as well as 5-LO mRNA expression. We identified two proximal Sp1/Sp3 ... [more ▼]

The histone deacetylase inhibitor trichostatin A (TsA) potently induces 5-lipoxygenase (5-LO) promoter activity in reporter gene assays as well as 5-LO mRNA expression. We identified two proximal Sp1/Sp3 binding sites in the 5-LO gene promoter mediating the TsA effect in both 5-LO-negative HeLa cells and in 5-LO expressing Mono Mac 6 (MM6) cells, the tandem GC-boxes, by contrast, were not important for the TsA effect. TsA neither altered the protein expression levels of Sp1/Sp3 nor of the histone deacetylases HDAC1/2, nor did it apparently change the protein complex formation by these factors. Also, treatment of cells with TsA did not change the binding affinity of Sp1/Sp3 in cell extracts, as tested by DAPA analysis using probes containing the proximal GC boxes. However, in the living cell TsA induced Sp1, Sp3 and RNA polymerase II recruitment to the 5-LO promoter without changing the acetylation status of histone protein H4. Cotransfection studies suggest that both Sp1 and Sp3 can mediate the TsA effect. This is the first report demonstrating that Sp3 is involved in the regulation of 5-LO promoter activity. In summary, we show that TsA increases 5-LO promoter activity by the enhanced recruitment of Sp1 and Sp3 to the 5-LO promoter. [less ▲]

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See detailModulation by cADPr of Ca2+ mobilization and oxidative response in dimethylsulfoxide- or retinoic acid-differentiated HL-60 cells
Bréchard, Sabrina UL; Brunello, A.; Bueb, Jean-Luc UL et al

in Biochimica et Biophysica Acta (2006), 1763(1), 129-36

In human phagocytic cells, reactive oxygen species (ROS) generation in response to N-formyl-L-Methionyl-L-Leucyl-L-Phenylalanine (fMLF) is largely dependent on cytosolic free calcium concentration ([Ca2 ... [more ▼]

In human phagocytic cells, reactive oxygen species (ROS) generation in response to N-formyl-L-Methionyl-L-Leucyl-L-Phenylalanine (fMLF) is largely dependent on cytosolic free calcium concentration ([Ca2+]i). Cyclic ADP-ribose (cADPr) is able to regulate Ca2+ release from intracellular stores through the ryanodine receptor but its potential role in biological responses has so far not been determined. In this study, we examined whether extracellular and intracellular cADPr is required in fMLF-induced [Ca2+]i rise and consequently in the oxidative response in human neutrophil-like HL-60 cells differentiated with dimethylsulfoxide or all-trans-retinoic acid (ATRA). We establish that extracellular cADPr cannot elicit [Ca2+]i elevation. Furthermore, we demonstrate that 8-Br-cADPr, a functional antagonist of cADPr, inhibits Ca2+ entry into HL-60 cells differentiated with ATRA and stimulated with fMLF (95+/-4 and 148+/-5 nM respectively, n=3). Finally, we show that this partial inhibition of Ca2+ mobilization is unrelated to ROS production (10.0+/-0.3 vs. 9.6+/-0.5 A.U., n=3). In conclusion, we showed that cADPr can control fMLF-induced Ca2+ influx but is unable to regulate a Ca2+-dependent biological response, i.e. H2O2 production. [less ▲]

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See detailReceptor-independent effects of natural cannabinoids in rat peritoneal mast cells in vitro
Bueb, Jean-Luc UL; Lambert, D. M.; Tschirhart, Eric UL

in Biochimica et Biophysica Acta (2001), 1538(2-3), 252-9

Cannabinoids can activate CB(1) and CB(2) receptors. Since a CB(2) mRNA has been described in rat peritoneal mast cells (RPMC), we investigated a series of cannabinoids and derivatives for their capacity ... [more ▼]

Cannabinoids can activate CB(1) and CB(2) receptors. Since a CB(2) mRNA has been described in rat peritoneal mast cells (RPMC), we investigated a series of cannabinoids and derivatives for their capacity to stimulate RPMC. Effects of natural cannabinoids Delta(9)-tetrahydrocannabinol (Delta(9)-THC), Delta(8)-THC, endocannabinoids (anandamide, palmitoylethanolamide) and related compounds (N-decanoyl-, N-lauroyl-, N-myristoyl-, N-stearoyl- and N-oleoyl-ethanolamines; N-palmitoyl derivatives (-butylamine, -cyclohexylamine, -isopropylamine); and N-palmitoyl, O-palmitoylethanolamine), and synthetic cannabinoids including WIN 55,212-2, SR141716A and SR144528 were assessed for their capacity to induce histamine release or prime RPMC stimulated by compound 48/80. Only Delta(9)-THC and Delta(8)-THC could induce non-lytic, energy- and concentration-dependent histamine releases from RPMC (respective EC(50) values: 23.5+/-1.2; 53.4+/-20.6 microM, and maxima: 71.2+/-5.5; 55.7+/-2.7% of the total RPMC histamine content). These were not blocked by CB(1) (SR141716A) or CB(2) (SR144528) antagonists, but reduced by pertussis toxin (100 ng/ml). Endocannabinoids and analogues did neither induce histamine secretion, nor prime secretion induced by compound 48/80 (0.2 microg/ml). Delta(9)-THC and Delta(8)-THC induced in vitro histamine secretion from RPMC through CB receptor-independent interactions, partly involving G(i/o) protein activation. [less ▲]

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See detailAnalogues and homologues of N-palmitoylethanolamide, a putative endogenous CB(2) cannabinoid, as potential ligands for the cannabinoid receptors
Lambert, D. M.; DiPaolo, F. G.; Sonveaux, P. et al

in Biochimica et Biophysica Acta (1999), 1440(2-3), 266-74

The presence of CB(2) receptors was reported in the rat basophilic cell line RBL-2H3 and N-palmitoylethanolamide was proposed as an endogenous, potent agonist of this receptor. We synthesized a series of ... [more ▼]

The presence of CB(2) receptors was reported in the rat basophilic cell line RBL-2H3 and N-palmitoylethanolamide was proposed as an endogenous, potent agonist of this receptor. We synthesized a series of 10 N-palmitoylethanolamide homologues and analogues, varying by the elongation of the fatty acid chain from caproyl to stearoyl and by the nature of the amide substituent, respectively, and evaluated the affinity of these compounds to cannabinoid receptors in the rat spleen, RBL-2H3 cells and CHO-CB(1) and CHO-CB(2) receptor-transfected cells. In rat spleen slices, CB(2) receptors were the predominant form of the cannabinoid receptors. No binding of [(3)H]SR141716A was observed. [(3)H]CP-55,940 binding was displaced by WIN 55,212-2 and anandamide. No displacement of [(3)H]CP-55,940 or [(3)H]WIN 55,212-2 by palmitoylethanolamide derivatives was observed in rat spleen slices. In RBL-2H3 cells, no binding of [(3)H]CP-55,940 or [(3)H]WIN 55,212-2 could be observed and conversely, no inhibitory activity of N-palmitoylethanolamide derivatives and analogues was measurable. These compounds do not recognize the human CB(1) and CB(2) receptors expressed in CHO cells. In conclusion, N-palmitoylethanolamide was, in our preparations, a weak ligand while its synthesized homologues or analogues were essentially inactive. Therefore, it seems unlikely that N-palmitoylethanolamide is an endogenous agonist of the CB(2) receptors but it may be a compound with potential therapeutic applications since it may act via other mechanisms than cannabinoid CB(1)-CB(2) receptor interactions. [less ▲]

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See detailA double-labelling fluorescent assay for concomitant measurements of [Ca2+]i and O2. production in human macrophages
Bueb, Jean-Luc UL; Gallois, A.; Schneider, J. C. et al

in Biochimica et Biophysica Acta (1995), 1244(1), 79-84

To measure intracellular free Ca2+ concentration ([Ca2+]i) and superoxide (O2) production in human alveolar macrophages, we used the fluorescent Ca2+ indicator fura-2 and the O2-sensitive dye ... [more ▼]

To measure intracellular free Ca2+ concentration ([Ca2+]i) and superoxide (O2) production in human alveolar macrophages, we used the fluorescent Ca2+ indicator fura-2 and the O2-sensitive dye dihydrorhodamine-123, which becomes fluorescent in its oxidized form, rhodamine-123. We describe a new double-dye technique whereby the kinetics of both [Ca2+]i levels and O2. production can be monitored simultaneously. This technique was developed in the dimethylsulfoxide-differentiated monocytic-like U-937 cell line (not equal to U-937), validated by comparison with single dye measurements and applied to human alveolar macrophages. The chemotactic peptide N-formyl-L-Methionyl-L-Leucyl-L-Phenylalanine induced in both cell types a similar transient elevation in [Ca2+]i, followed within seconds by a sustained increase in O2 production, which was however 4-fold weaker in not equal to U-937 cells. These results indicate that O2 production is an early event following the stimulation of human alveolar macrophages. This new double-dye technique may be relevant to other O2 ion-producing cells and could help to define more precisely the kinetics of the events leading to this biological response. [less ▲]

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