The Experts below are selected from a list of 147 Experts worldwide ranked by ideXlab platform
Melissa Rungemorris - One of the best experts on this subject based on the ideXlab platform.
-
transactivation of glucocorticoid inducible rat Aryl Sulfotransferase sult1a1 gene transcription
Drug Metabolism and Disposition, 2003Co-Authors: Hai Lin Fang, Zhengbo Duanmu, Thomas A. Kocarek, Sarita D Shenoy, Melissa RungemorrisAbstract:The purpose of the current study was to establish the role of the glucocorticoid receptor (GR) and androgen receptor (AR) transcription factors in the transactivation of rat Aryl Sulfotransferase (SULT1A1) gene transcription and to identify the functional hormone-responsive element(s) in the SULT1A1 gene. A cis-acting inverted repeat with three intervening bases (IR3) was identified in the 5-flanking of the SULT1A1 gene that mediates the transactivation of SULT1A1 gene transcription by both the GR and AR. CV-1 cells were cotransfected with SULT1A1-luciferase reporter plasmids and either wild-type or mutant GR or AR expression constructs. In cotransfectants expressing the wild-type GR, treatment with triamcinolone acetonide produced an 4- to 6-fold induction of luciferase activity in IR3-containing SULT1A1 reporter plasmids. IR3-containing SULT1A1 reporter constructs were also activated by treatment with the synthetic androgen R1881 in cells cotransfected with wild-type but not mutant AR. In primary cultured rat hepatocytes, androgen-inducible expression of IR3-containing SULT1A1 reporter plasmids required cotransfection with AR expression plasmid. Targeted disruption of the SULT1A1 IR3 by mutation of a conserved GT sequence in the 3 half-site of the element ablated GR and AR responsiveness. These results indicate that a proximal IR3 element in the 5-flanking region of the rat SULT1A1 gene is sufficient for the transactivation of SULT1A1 gene transcription by the GR and AR, and that relative to the GR, functional AR activity is reduced in primary cultured rat hepatocytes.
-
effects of dexamethasone on Aryl sult1a1 and hydroxysteroid sult2a1 Sulfotransferase gene expression in primary cultured human hepatocytes
Drug Metabolism and Disposition, 2002Co-Authors: Zhengbo Duanmu, Thomas A. Kocarek, C N Falany, Deborah Locke, J R Smigelski, Michael S Dahn, Melissa RungemorrisAbstract:To determine whether the dexamethasone (DEX)-inducible hepatic Sulfotransferase gene expression that has been described in the rat is conserved in humans, the effects of DEX treatment on hydroxysteroid Sulfotransferase (SULT2A1) and Aryl Sulfotransferase (SULT1A1) gene expression were investigated in primary cultured human hepatocytes. Hepatocytes were prepared from nontransplantable human livers by collagenase perfusion of the left hepatic lobe, and cultured in Williams9 medium E that was supplemented with 0.25 U/ml insulin. As reported in the rat, DEX treatment produced concentration-dependent increases in SULT2A1 mRNA and protein expression, with maximum increases observed at concentrations of DEX that would be expected to activate the pregnane X receptor (PXR) transcription factor. In contrast to the rat, in which DEX-inducible SULT1A1 expression has been demonstrated, SULT1A1 expression in primary cultured human hepatocytes was not measurably increased by DEX. In transient transfections conducted in primary cultured rat hepatocytes, the PXR ligands DEX and pregnenolone-16α-carbonitrile significantly induced transcription of human and rat SULT2A reporter gene constructs. Cotransfection of either the human or rat SULT2A reporter gene with a PXR dominant negative construct significantly reduced DEX-inducible transcription. These results underscore that while certain features of rat hepatic Sulfotransferase gene regulation are conserved in humans, important differences exist across species. The findings also implicate a role for the PXR transcription factor in DEX-inducible rat and human SULT2A gene expression.
-
transcriptional regulation of rat hepatic Aryl Sulfotransferase sult1a1 gene expression by glucocorticoids
Drug Metabolism and Disposition, 2001Co-Authors: Zhengbo Duanmu, Thomas A. Kocarek, Melissa RungemorrisAbstract:The 5*-flanking region [1892 base pairs (bp)] of the rat Aryl Sulfotransferase (SULT1A1) gene was cloned and the cis-acting sequences involved in glucocorticoid-inducible SULT1A1 gene transcription were characterized. SULT1A1 promoter and 5*-flanking sequences lacked a TATA box and a consensus glucocorticoid response element. Using a 5*-rapid amplification of cDNA ends approach, four SULT1A1 transcription start sites were identified. Transient transfection studies with SULT1A1-5*:luciferase reporter constructs in primary cultured rat hepatocytes revealed that treatment with the potent glucocorticoid dexamethasone (10 29 ‐10 25 M) produced concentration-dependent increases in luciferase activity in constructs containing from 1892 to 119 bp of the SULT1A1 5*-flanking region. Relative to the most upstream SULT1A1 transcription start site, the minimal cis-acting sequences that were required for dexamethasone-inducible SULT1A1 expression were located between 284 and 269 bp. Treatment of transfectants with a panel of steroids, including dexamethasone, triamcinolone acetonide, hydrocortisone, dihydrotestosterone, 17b-estradiol, and pregnenolone-16a-carbonitrile, revealed that steroid-inducible SULT1A1 gene expression was specific for glucocorticoid-class steroids. Concentration-response studies, coupled with a robust inhibition of glucocorticoid-inducible SULT1A1-5*:luciferase reporter activity by antiglucocorticoid/antiprogestin RU-486, recapitulated earlier findings on endogenous SULT1A1 gene expression and implicated a major role for the glucocorticoid receptor transcription factor in the regulation of glucocorticoid-inducible SULT1A1 gene expression.
-
induction of rat hepatic Aryl Sulfotransferase sult1a1 gene expression by triamcinolone acetonide impact on minoxidil mediated hypotension
Toxicology and Applied Pharmacology, 2000Co-Authors: Zhengbo Duanmu, C N Falany, Joseph C Dunbar, Melissa RungemorrisAbstract:Abstract The hypotensive agent minoxidil (6-imino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine) depends upon Aryl Sulfotransferase (SULT1)-catalyzed sulfation for its bioactivation. Previous reports suggest that glucocorticoids induce class-specific SULT1 and isoform-specific SULT1A1 gene expression in rat liver. In the present study, rats were treated with the glucocorticoid triamcinolone acetonide (TA, 5 mg/kg/day ip × 3 days) or its vehicle, 2% Tween-20, prior to minoxidil, and subsequent effects on mean arterial pressure (MAP), heart rate (HR), and hepatic SULT1 gene expression were characterized. Minoxidil treatment (1.5 mg/kg) resulted in a steady decline in MAP values of 16.3 to 18.6% relative to basal control levels at 35 to 60 min following minoxidil injection. Pentachlorophenol (PCP, 40 μmol/kg ip), an inhibitor of SULT1 enzyme activity, effectively ablated the hypotensive effects of minoxidil. By contrast, pretreatment with TA significantly enhanced minoxidil-induced hypotension. Relative to vehicle-treated controls, TA-treated rats displayed a steeper rate of decline in MAP and more profound levels of hypotension with decreases in MAP following minoxidil administration of 27.8%. TA also produced significant increases in hepatic SULT1 mRNA expression (of 271%) and SULT1A1 immunoreactive protein levels (of 273%), relative to vehicle-treated controls. These results provide physiological evidence to support the biological relevance of SULT1A1 induction by glucocorticoids. The data indicate that steroid treatment induces SULT1A1 gene expression and, as a consequence, accentuates the hypotensive effects of minoxidil.
Zhengbo Duanmu - One of the best experts on this subject based on the ideXlab platform.
-
transactivation of glucocorticoid inducible rat Aryl Sulfotransferase sult1a1 gene transcription
Drug Metabolism and Disposition, 2003Co-Authors: Hai Lin Fang, Zhengbo Duanmu, Thomas A. Kocarek, Sarita D Shenoy, Melissa RungemorrisAbstract:The purpose of the current study was to establish the role of the glucocorticoid receptor (GR) and androgen receptor (AR) transcription factors in the transactivation of rat Aryl Sulfotransferase (SULT1A1) gene transcription and to identify the functional hormone-responsive element(s) in the SULT1A1 gene. A cis-acting inverted repeat with three intervening bases (IR3) was identified in the 5-flanking of the SULT1A1 gene that mediates the transactivation of SULT1A1 gene transcription by both the GR and AR. CV-1 cells were cotransfected with SULT1A1-luciferase reporter plasmids and either wild-type or mutant GR or AR expression constructs. In cotransfectants expressing the wild-type GR, treatment with triamcinolone acetonide produced an 4- to 6-fold induction of luciferase activity in IR3-containing SULT1A1 reporter plasmids. IR3-containing SULT1A1 reporter constructs were also activated by treatment with the synthetic androgen R1881 in cells cotransfected with wild-type but not mutant AR. In primary cultured rat hepatocytes, androgen-inducible expression of IR3-containing SULT1A1 reporter plasmids required cotransfection with AR expression plasmid. Targeted disruption of the SULT1A1 IR3 by mutation of a conserved GT sequence in the 3 half-site of the element ablated GR and AR responsiveness. These results indicate that a proximal IR3 element in the 5-flanking region of the rat SULT1A1 gene is sufficient for the transactivation of SULT1A1 gene transcription by the GR and AR, and that relative to the GR, functional AR activity is reduced in primary cultured rat hepatocytes.
-
effects of dexamethasone on Aryl sult1a1 and hydroxysteroid sult2a1 Sulfotransferase gene expression in primary cultured human hepatocytes
Drug Metabolism and Disposition, 2002Co-Authors: Zhengbo Duanmu, Thomas A. Kocarek, C N Falany, Deborah Locke, J R Smigelski, Michael S Dahn, Melissa RungemorrisAbstract:To determine whether the dexamethasone (DEX)-inducible hepatic Sulfotransferase gene expression that has been described in the rat is conserved in humans, the effects of DEX treatment on hydroxysteroid Sulfotransferase (SULT2A1) and Aryl Sulfotransferase (SULT1A1) gene expression were investigated in primary cultured human hepatocytes. Hepatocytes were prepared from nontransplantable human livers by collagenase perfusion of the left hepatic lobe, and cultured in Williams9 medium E that was supplemented with 0.25 U/ml insulin. As reported in the rat, DEX treatment produced concentration-dependent increases in SULT2A1 mRNA and protein expression, with maximum increases observed at concentrations of DEX that would be expected to activate the pregnane X receptor (PXR) transcription factor. In contrast to the rat, in which DEX-inducible SULT1A1 expression has been demonstrated, SULT1A1 expression in primary cultured human hepatocytes was not measurably increased by DEX. In transient transfections conducted in primary cultured rat hepatocytes, the PXR ligands DEX and pregnenolone-16α-carbonitrile significantly induced transcription of human and rat SULT2A reporter gene constructs. Cotransfection of either the human or rat SULT2A reporter gene with a PXR dominant negative construct significantly reduced DEX-inducible transcription. These results underscore that while certain features of rat hepatic Sulfotransferase gene regulation are conserved in humans, important differences exist across species. The findings also implicate a role for the PXR transcription factor in DEX-inducible rat and human SULT2A gene expression.
-
transcriptional regulation of rat hepatic Aryl Sulfotransferase sult1a1 gene expression by glucocorticoids
Drug Metabolism and Disposition, 2001Co-Authors: Zhengbo Duanmu, Thomas A. Kocarek, Melissa RungemorrisAbstract:The 5*-flanking region [1892 base pairs (bp)] of the rat Aryl Sulfotransferase (SULT1A1) gene was cloned and the cis-acting sequences involved in glucocorticoid-inducible SULT1A1 gene transcription were characterized. SULT1A1 promoter and 5*-flanking sequences lacked a TATA box and a consensus glucocorticoid response element. Using a 5*-rapid amplification of cDNA ends approach, four SULT1A1 transcription start sites were identified. Transient transfection studies with SULT1A1-5*:luciferase reporter constructs in primary cultured rat hepatocytes revealed that treatment with the potent glucocorticoid dexamethasone (10 29 ‐10 25 M) produced concentration-dependent increases in luciferase activity in constructs containing from 1892 to 119 bp of the SULT1A1 5*-flanking region. Relative to the most upstream SULT1A1 transcription start site, the minimal cis-acting sequences that were required for dexamethasone-inducible SULT1A1 expression were located between 284 and 269 bp. Treatment of transfectants with a panel of steroids, including dexamethasone, triamcinolone acetonide, hydrocortisone, dihydrotestosterone, 17b-estradiol, and pregnenolone-16a-carbonitrile, revealed that steroid-inducible SULT1A1 gene expression was specific for glucocorticoid-class steroids. Concentration-response studies, coupled with a robust inhibition of glucocorticoid-inducible SULT1A1-5*:luciferase reporter activity by antiglucocorticoid/antiprogestin RU-486, recapitulated earlier findings on endogenous SULT1A1 gene expression and implicated a major role for the glucocorticoid receptor transcription factor in the regulation of glucocorticoid-inducible SULT1A1 gene expression.
-
induction of rat hepatic Aryl Sulfotransferase sult1a1 gene expression by triamcinolone acetonide impact on minoxidil mediated hypotension
Toxicology and Applied Pharmacology, 2000Co-Authors: Zhengbo Duanmu, C N Falany, Joseph C Dunbar, Melissa RungemorrisAbstract:Abstract The hypotensive agent minoxidil (6-imino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine) depends upon Aryl Sulfotransferase (SULT1)-catalyzed sulfation for its bioactivation. Previous reports suggest that glucocorticoids induce class-specific SULT1 and isoform-specific SULT1A1 gene expression in rat liver. In the present study, rats were treated with the glucocorticoid triamcinolone acetonide (TA, 5 mg/kg/day ip × 3 days) or its vehicle, 2% Tween-20, prior to minoxidil, and subsequent effects on mean arterial pressure (MAP), heart rate (HR), and hepatic SULT1 gene expression were characterized. Minoxidil treatment (1.5 mg/kg) resulted in a steady decline in MAP values of 16.3 to 18.6% relative to basal control levels at 35 to 60 min following minoxidil injection. Pentachlorophenol (PCP, 40 μmol/kg ip), an inhibitor of SULT1 enzyme activity, effectively ablated the hypotensive effects of minoxidil. By contrast, pretreatment with TA significantly enhanced minoxidil-induced hypotension. Relative to vehicle-treated controls, TA-treated rats displayed a steeper rate of decline in MAP and more profound levels of hypotension with decreases in MAP following minoxidil administration of 27.8%. TA also produced significant increases in hepatic SULT1 mRNA expression (of 271%) and SULT1A1 immunoreactive protein levels (of 273%), relative to vehicle-treated controls. These results provide physiological evidence to support the biological relevance of SULT1A1 induction by glucocorticoids. The data indicate that steroid treatment induces SULT1A1 gene expression and, as a consequence, accentuates the hypotensive effects of minoxidil.
Giulio Tononi - One of the best experts on this subject based on the ideXlab platform.
-
gene expression in the brain across the sleep waking cycle
Brain Research, 2000Co-Authors: Cecilia Cirelli, Giulio TononiAbstract:Sleep and waking differ significantly in terms of behavior, metabolism, and neuronal activity. Recent evidence indicates that sleep and waking also differ with respect to the expression of certain genes. To systematically investigate such changes, we used mRNA differential display and cDNA microarrays to screen ∼10 000 transcripts expressed in the cerebral cortex of rats after 8 h of sleep, spontaneous waking, or sleep deprivation. We found that 44 genes had higher mRNA levels after waking and/or sleep deprivation relative to sleep, while 10 were upregulated after sleep. Known genes that were upregulated in waking and sleep deprivation can be grouped into the following categories: immediate early genes/transcription factors (Arc, CHOP, IER5, NGFI-A, NGFI-B, N-Ras, Stat3), genes related to energy metabolism (glucose type I transporter Glut1, Vgf), growth factors/adhesion molecules (BDNF, TrkB, F3 adhesion molecule), chaperones/heat shock proteins (BiP, ERP72, GRP75, HSP60, HSP70), vesicle- and synapse-related genes (chromogranin C, synaptotagmin IV), neurotransmitter/hormone receptors (adrenergic receptor α1A and β2, GABAA receptor β3, glutamate NMDA receptor 2A, glutamate AMPA receptor GluR2 and GluR3, nicotinic acetylcholine receptor β2, thyroid hormone receptor TRβ), neurotransmitter transporters (glutamate/aspartate transporter GLAST, Na+/Cl− transporter NTT4/Rxt1), enzymes (Aryl Sulfotransferase, c-jun N-terminal kinase 1, serum/glucocorticoid-induced serine/threonine kinase), and a miscellaneous group (calmodulin, cyclin D2, LMO-4, metallothionein 3). Several other genes that were upregulated in waking and all the genes upregulated in sleep, with the exception of the one coding for membrane protein E25, did not match any known sequence. Thus, significant changes in gene expression occur across behavioral states, which are likely to affect basic cellular functions such as RNA and protein synthesis, neural plasticity, neurotransmission, and metabolism.
-
gene expression in the brain across the sleep waking cycle
Brain Research, 2000Co-Authors: Cecilia Cirelli, Giulio TononiAbstract:Sleep and waking differ significantly in terms of behavior, metabolism, and neuronal activity. Recent evidence indicates that sleep and waking also differ with respect to the expression of certain genes. To systematically investigate such changes, we used mRNA differential display and cDNA microarrays to screen approximately 10000 transcripts expressed in the cerebral cortex of rats after 8 h of sleep, spontaneous waking, or sleep deprivation. We found that 44 genes had higher mRNA levels after waking and/or sleep deprivation relative to sleep, while 10 were upregulated after sleep. Known genes that were upregulated in waking and sleep deprivation can be grouped into the following categories: immediate early genes/transcription factors (Arc, CHOP, IER5, NGFI-A, NGFI-B, N-Ras, Stat3), genes related to energy metabolism (glucose type I transporter Glut1, Vgf), growth factors/adhesion molecules (BDNF, TrkB, F3 adhesion molecule), chaperones/heat shock proteins (BiP, ERP72, GRP75, HSP60, HSP70), vesicle- and synapse-related genes (chromogranin C, synaptotagmin IV), neurotransmitter/hormone receptors (adrenergic receptor alpha(1A) and beta(2), GABA(A) receptor beta(3), glutamate NMDA receptor 2A, glutamate AMPA receptor GluR2 and GluR3, nicotinic acetylcholine receptor beta(2), thyroid hormone receptor TRbeta), neurotransmitter transporters (glutamate/aspartate transporter GLAST, Na(+)/Cl(-) transporter NTT4/Rxt1), enzymes (Aryl Sulfotransferase, c-jun N-terminal kinase 1, serum/glucocorticoid-induced serine/threonine kinase), and a miscellaneous group (calmodulin, cyclin D2, LMO-4, metallothionein 3). Several other genes that were upregulated in waking and all the genes upregulated in sleep, with the exception of the one coding for membrane protein E25, did not match any known sequence. Thus, significant changes in gene expression occur across behavioral states, which are likely to affect basic cellular functions such as RNA and protein synthesis, neural plasticity, neurotransmission, and metabolism.
Emerich S. Fiala - One of the best experts on this subject based on the ideXlab platform.
-
N2-amination of guanine to 2-hydrazinohypoxanthine, a novel in vivo nucleic acid modification produced by the hepatocarcinogen 2-nitropropane.
Chemical Research in Toxicology, 1998Co-Authors: Rama S. Sodum, Emerich S. FialaAbstract:2-Nitropropane, an industrial chemical and a hepatocarcinogen in rats, induces Aryl Sulfotransferase-mediated liver DNA and RNA base modifications [Sodum, R. S., Sohn, O. S., Nie, G., and Fiala, E....
-
Activation of the liver carcinogen 2-nitropropane by Aryl Sulfotransferase.
Chemical Research in Toxicology, 1994Co-Authors: Rama S. Sodum, Ock Soon Sohn, Guo Nie, Emerich S. FialaAbstract:8-Aminoguanine had previously been identified as one of the nucleic acid base modifications produced in livers of rats by treatment with the hepatocarcinogen 2-nitropropane (2-NP), and a hypothetical mechanism of activation of 2-NP to hydroxylamine-O-sulfonate or acetate that would lead to NH2+, an aminating species, was proposed [Sodum et al. (1993) Chem. Res. Toxicol. 6, 269-276]. We now present in vivo and in vitro experimental evidence for the activation of 2-NP to an aminating species by rat liver Aryl Sulfotransferase. Pretreatment of rats with the Aryl Sulfotransferase inhibitors pentachlorophenol or 2,6-dichloro-4-nitrophenol significantly decreased the levels of liver nucleic acid modifications produced by 2-NP treatment. Furthermore, partially purified rat liver Aryl Sulfotransferase was shown to activate 2-NP and 2-NP nitronate in vitro at neutral pH and 37 degrees C, to a reactive species that aminated guanosine at the C8 position. This activation was dependent on the presence of the enzyme, its specific cofactor adenosine 3'-phosphate 5'-phosphosulfate, and mercaptoethanol. As in the case of the in vitro studies, pentachlorophenol and 2,6-dichloro-4-nitrophenol inhibited the in vitro formation of 8-aminoguanosine and 8-oxoguanosine. The corresponding primary nitroalkane, 1-nitropropane, which is not mutagenic and does not appear to be carcinogenic, was not a substrate for Aryl Sulfotransferase in the in vitro amination of guanosine.
Erwan Ar Gall - One of the best experts on this subject based on the ideXlab platform.
-
Constitutive or Inducible Protective Mechanisms against UV-B Radiation in the Brown Alga Fucus vesiculosus? A Study of Gene Expression and Phlorotannin Content Responses
PLoS ONE, 2015Co-Authors: Emeline Creis, Ludovic Delage, Catherine Leblanc, Sophie Goulitquer, Sophie Charton, Philippe Potin, Erwan Ar GallAbstract:A role as UV sunscreens has been suggested for phlorotannins, the phenolic compounds that accumulate in brown algae in response to a number of external stimuli and take part in cell wall structure. After exposure of the intertidal brown alga Fucus vesiculosus to artificial UV-B radiation, we examined its physiological responses by following the transcript level of the pksIII gene encoding a phloroglucinol synthase, likely to be involved in the first step of phlorotannins biosynthesis. We also monitored the expression of three targeted genes, encoding a heat shock protein (hsp70), which is involved in global stress responses, an Aryl Sulfotransferase (ast), which could be involved in the sulfation of phlorotannins, and a vanadium bromoperoxidase (vbpo), which can potentially participate in the scavenging of Reactive Oxygen Species (ROS) and in the cross-linking and condensation of phlorotannins. We investigated whether transcriptional regulation of these genes is correlated with an induction of phlorotannin accumulation by establishing metabolite profiling of purified fractions of low molecular weight phlorotannins. Our findings demonstrated that a high dose of UV-B radiation induced a significant overexpression of hsp70 after 12 and 24 hours following the exposure to the UV-B treatment, compared to control treatment. The physiological performance of algae quantified by the photosynthetic efficiency (Fv/Fm) was slightly reduced. However UV-B treatment did not induce the accumulation of soluble phlorotannins in F. vesiculosus during the kinetics of four weeks, a result that may be related to the lack of induction of the pksIII gene expression. Taken together these results suggest a constitutive accumulation of phlorotannins occurring during the development of F.vesiculosus, rather than inducible processes. Gene expression studies and phlorotannin profiling provide here complementary approaches to global quantifications currently used in studies of phenolic compounds in brown algae.
