Search results for " Regulation"
showing 10 items of 3187 documents
Evaluation of the IKKβ Binding of Indicaxanthin by Induced-Fit Docking, Binding Pose Metadynamics, and Molecular Dynamics
2021
Background: Indicaxanthin, a betaxanthin belonging to the betalain class of compounds, has been recently demonstrated to exert significant antiproliferative effects inducing apoptosis of human melanoma cells through the inhibition of NF-κB as the predominant pathway. Specifically, Indicaxanthin inhibited IκBα degradation in A375 cells. In resting cells, NF-κB is arrested in the cytoplasm by binding to its inhibitor protein IκBα. Upon stimulation, IκBα is phosphorylated by the IKK complex, and degraded by the proteasome, liberating free NF-κB into the nucleus to initiate target gene transcription. Inhibition of the IKK complex leads to the arrest of the NF-κB pathway.Methods: To acquire deta…
Transcriptional regulation and expression of CYP3A4 in hepatocytes.
2007
CYP3A4 is the most abundantly expressed drug-metabolizing P450 enzyme in human liver and contributes to the metabolism of a large number of drugs in use today. CYP3A4 is constitutively expressed in adult hepatocytes but it can also be transcriptionally induced by a variety of structurally diverse xenochemicals. CYP3A4 strongly contributes to the important variability in the therapeutic and toxic effects of drugs owing to the major role it plays in xenobiotic metabolism and the large intra- and inter-individual variability to which it is subjected. The functional examination of up to 13 kb of the CYP3A4 5'-flanking region has revealed that the regulation of this gene is a complex issue, with…
PPARα/HNF4α Interplay on Diversified Responsive Elements. Relevance in the Regulation of Liver Peroxisomal Fatty Acid Catabolism
2012
In mammals, the liver is the major organ of fatty acid catabolism. This pathway is involved in both mitochondria and peroxisome. While mitochondria breaks down fatty acids with short, medium and long carbon chains, peroxisomes are involved in the catabolism of very long and branched chain fatty acids, which are degraded by three enzymes: acyl-CoA oxidase, multifunctional enzyme and thiolase enzyme. The active pathway results mainly from a tight transcriptional control of these gene-encoding enzymes. Two major nuclear receptors that are highly expressed in this organ are involved in this control, e.g. PPARα (peroxisome proliferator-activated receptor, α isoform) and HNF4α (hepatic nuclear fa…
Furosemide interactions with brain GABAA receptors
1997
1. The loop diuretic furosemide is known to antagonize the function of gamma-aminobutyric acid type A (GABAA) receptors. The purpose of the present study was to examine the direct interaction of furosemide with the GABAA receptors by autoradiography and ligand binding studies with native rat and human receptors and with recombinant receptors composed of rat subunits. 2. Autoradiography with [35S]-t-butylbicyclophosphorothionate ([35S]-TBPS) as a ligand indicated that furosemide (0.1-1 mM) reversed the 5 microM GABA-induced inhibition of binding only in the cerebellar granule cell layer of rat brain sections. In all other regions studied, notably also in the hippocampal and thalamic areas, f…
Regulation of Phenotypic Switching and Heterogeneity in Photorhabdus luminescens Cell Populations.
2019
Phenotypic heterogeneity in bacterial cell populations allows genetically identical organisms to different behavior under similar environmental conditions. The Gram-negative bacterium Photorhabdus luminescens is an excellent organism to study phenotypic heterogeneity since their life cycle involves a symbiotic interaction with soil nematodes as well as a pathogenic association with insect larvae. Phenotypic heterogeneity is highly distinct in P. luminescens. The bacteria exist in two phenotypic forms that differ in various morphologic and phenotypic traits and are therefore distinguished as primary (1°) and secondary (2°) cells. The 1 cells are bioluminescent, pigmented, produce several sec…
Pho85 and PI(4,5)P(2) regulate different lipid metabolic pathways in response to cold
2019
Lipid homeostasis allows cells to adjust membrane biophysical properties in response to changes in environmental conditions. In the yeast Saccharomyces cerevisiae, a downward shift in temperature from an optimal reduces membrane fluidity, which triggers a lipid remodeling of the plasma membrane. How changes in membrane fluidity are perceived, and how the abundance and composition of different lipid classes is properly balanced, remain largely unknown. Here, we show that the levels of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], the most abundant plasma membrane phosphoinositide, drop rapidly in response to a downward shift in temperature. This change triggers a signaling cascade trans…
Differential gene expression in p53-mediated G(1) arrest of human fibroblasts after gamma-irradiation or N-phosphoacetyl-L-aspartate treatment.
2000
In human fibroblasts, N:-phosphoacetyl-L-aspartate (PALA) and gamma-radiation induce reversible and irreversible p53-mediated G(1) cell cycle arrest, respectively. By coupling the premature chromosome condensation technique to fluorescence in situ hybridization, we found no evidence of DNA damage after PALA treatment. We used representational difference analysis (cDNA-RDA) to study changes in gene expression after PALA treatment and gamma-radiation in normal human fibroblasts. The mammary-derived growth inhibitor (MDGI) gene was expressed in PALA-treated cells. Ectopic MDGI expression arrested PALA-treated but not irradiated RKO cells. Expression of an antisense RNA against MDGI resulted in…
AAV-Mediated Clarin-1 Expression in the Mouse Retina: Implications for USH3A Gene Therapy
2015
Usher syndrome type III (USH3A) is an autosomal recessive disorder caused by mutations in clarin-1 (CLRN1) gene, leading to progressive retinal degeneration and sensorineural deafness. Efforts to develop therapies for preventing photoreceptor cell loss are hampered by the lack of a retinal phenotype in the existing USH3 mouse models and by conflicting reports regarding the endogenous retinal localization of clarin-1, a transmembrane protein of unknown function. In this study, we used an AAV-based approach to express CLRN1 in the mouse retina in order to determine the pattern of its subcellular localization in different cell types. We found that all major classes of retinal cells express AAV…
Functioning of DcuC as the C 4 -Dicarboxylate Carrier during Glucose Fermentation by Escherichia coli
1999
ABSTRACT The dcuC gene of Escherichia coli encodes an alternative C 4 -dicarboxylate carrier (DcuC) with low transport activity. The expression of dcuC was investigated. dcuC was expressed only under anaerobic conditions; nitrate and fumarate caused slight repression and stimulation of expression, respectively. Anaerobic induction depended mainly on the transcriptional regulator FNR. Fumarate stimulation was independent of the fumarate response regulator DcuR. The expression of dcuC was not significantly inhibited by glucose, assigning a role to DcuC during glucose fermentation. The inactivation of dcuC increased fumarate-succinate exchange and fumarate uptake by DcuA and DcuB, suggesting a…
Regulation of aerobic and anaerobic D-malate metabolism of Escherichia coli by the LysR-type regulator DmlR (YeaT).
2010
ABSTRACT Escherichia coli K-12 is able to grow under aerobic conditions on d -malate using DctA for d -malate uptake and the d -malate dehydrogenase DmlA (formerly YeaU) for converting d -malate to pyruvate. Induction of dmlA encoding DmlA required an intact dmlR (formerly yeaT ) gene, which encodes DmlR, a LysR-type transcriptional regulator. Induction of dmlA by DmlR required the presence of d -malate or l - or meso -tartrate, but only d -malate supported aerobic growth. The regulator of general C 4 -dicarboxylate metabolism (DcuS-DcuR two-component system) had some effect on dmlA expression. The anaerobic l -tartrate regulator TtdR or the oxygen sensors ArcB-ArcA and FNR did not have a m…