Abstract:
:The transcription factor networks that regulate basal and xenobiotic-modulated expression of the hepatic sulfotransferases affect the dynamics of xenobiotic detoxication, carcinogen bioactivation and metabolic homeostasis. Emerging evidence suggests that liver-enriched transcription factors, the aryl hydrocarbon (Ah) receptor and members of the nuclear receptor transcription factor superfamily all play integrated roles in the control of sulfotransferase gene transcription. Unlike the well known up-regulation of CYP1A1, expression of rat hepatic aryl (SULT1A1) and hydroxysteroid (SULT2A) sulfotransferase is suppressed in response to treatment with the prototypic Ah receptor ligand, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin. Glucocorticoid-inducible rat hepatic SULT1A1 gene transcription occurs through a glucocorticoid receptor (GR)-mediated mechanism, while human hepatic SULT1A1 does not display GR-inducible expression. By comparison, liver-enriched transcription factors, such as CCAAT/enhancer binding protein, are essential for the maintenance of basal and GR-inducible rat hepatic SULT2A expression. The transcriptional control of rodent and human hepatic SULT2A expression is subject to trans-activation by the environmental sensor, pregnane X receptor (PXR). IR0 (inverted repeat with zero intervening bases) motifs located in the 5'-flanking regions of rodent SULT2A genes are required for transcriptional activation by PXR and other nuclear receptors, including constitutive androstane receptor, farnesoid X receptor and vitamin D receptor. Peroxisome proliferator activated receptor alpha (PPARalpha) mediates the induction of human, but not rat, hepatic SULT2A gene transcription, thus implicating a role for fatty acids as endogenous regulators of hepatic sulfonation in humans. This review focuses on the xenobiotic sensors and transcription factor systems that regulate sulfotransferase gene expression.
journal_name
Curr Drug Metabjournal_title
Current drug metabolismauthors
Runge-Morris M,Kocarek TAdoi
10.2174/1389200054633871keywords:
subject
Has Abstractpub_date
2005-08-01 00:00:00pages
299-307issue
4eissn
1389-2002issn
1875-5453journal_volume
6pub_type
杂志文章,评审abstract::New chemical entities are routinely screened in vitro and in vivo for their ability to induce cytochrome P450s (CYP), other drug-metabolizing enzymes and possibly transporters in an attempt to more accurately predict clinical parameters such as drug-drug interactions and clearance in humans. Some of these potential th...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200033489352
更新日期:2003-10-01 00:00:00
abstract::Maternal antenatal therapy with glucocorticoids (GC) is routinely used to prevent lung immaturity. The potential harmful effects on other organs, including in particular the central nervous system (CNS), are still controversial. In the present review we aimed to investigate: i) the beneficial and detrimental effects o...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:
更新日期:2013-02-01 00:00:00
abstract:BACKGROUND:Medical application of nanotechnology is termed as Nanomedicine and is widely used in healthcare industries. Nanotechnology has helped Physicians, Scientists and Technologists to understand the changes in cellular levels to develop nanomedicines and address the challenges faced by the healthcare sectors. Nan...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666180305154119
更新日期:2018-01-01 00:00:00
abstract::The pharmacological effects of a drug are highly dependent on the absorption, metabolism, elimination, and distribution of the drug. In the past few years it has become apparent that transport proteins play a major role in regulating the distribution, elimination and metabolism of some drugs. As a consequence of our n...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200023337559
更新日期:2002-06-01 00:00:00
abstract::This paper reviews the metabolism of new designer drugs of abuse that have emerged on the black market during the last years and is an update of a review published in 2005. The presented review contains data concerning the so-called 2C compounds (phenethylamine type) such as 4-bromo-2,5-dimethoxy-beta-phenethylamine (...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920010791526042
更新日期:2010-06-01 00:00:00
abstract::Drug metabolite identification and metabolic characteristics analysis play a crucial role in new drug research and development, because they can lead to varied efficacy, severe adverse reactions, and even toxicity. Classical methodologies for metabolite identification have mainly been based on mass spectrometry (MS) c...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200216666141230105649
更新日期:2014-01-01 00:00:00
abstract::Several epidemiological studies throughout the years have suggested that polyphenols from fruits and vegetables promote health and reduce the risk of certain chronic and neurodegenerative diseases. Yet, it has been proved to be extremely difficult to quantitatively establish the benefit afforded by polyphenols, princi...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200214666131210144115
更新日期:2014-01-01 00:00:00
abstract::Arylamine N-acetyltransferases (NAT) are xenobiotic-metabolizing enzymes responsible for the acetylation of many aromatic arylamine and heterocyclic amines, thereby playing an important role in both detoxification and activation of numerous drugs and carcinogens. Two closely related isoforms (NAT1 and NAT2) have been ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008784892092
更新日期:2008-07-01 00:00:00
abstract::Diabetes is associated with an increase risk for cardiovascular disease (CVD). Recently, macrovascular complications of diabetes have been shown to start before the development of diabetes. Indeed, several clinical studies have confirmed the increased risk of CVD in patients with impaired glucose tolerance (IGT). Sinc...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920009787522133
更新日期:2009-02-01 00:00:00
abstract::During the lifetime, our cells encounter many challenges to their own existence. The survival of organisms and cells depends on the interplay within a complex, yet precisely orchestrated network of proteins. Since the discovery of the Rel/NF-kappaB family of transcription factors, the research has never come to a stop...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920010791196283
更新日期:2010-03-01 00:00:00
abstract::The occurrence of idiosyncratic adverse drug reactions during late clinical trials or after a drug has been released can lead to a severe restriction in its use and even in its withdrawal. Metabolic activation of relatively inert functional groups to reactive electrophilic intermediates is considered to be an obligato...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200054021799
更新日期:2005-06-01 00:00:00
abstract::Part I of this article published in the previous issue of Current Drug Metabolism discussed the substrate specificity, inhibitor selectivity and structure-activity relationship (SAR) of human CYP2C9. The features of CYP2C9 pharmacophore and SAR models have been elaborated. Part II of this article will address the homo...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920009790820101
更新日期:2009-12-01 00:00:00
abstract::For the pharmaceutical industry, one of the challenges in evaluating the risk of future compound attrition at the discovery stage is the successful prediction of the major routes of clearance in humans. For compounds cleared by metabolism, such information will help to avoid the development of compounds that will exhi...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200033489235
更新日期:2003-12-01 00:00:00
abstract:BACKGROUND:Drug-induced cholestasis is a risk factor in the progression of drug candidates, and poses a serious health hazard if not detected before going into a human. Intrahepatic accumulation of Bile Acids (BAs) represents a characteristic phenomenon associated with drug-induced cholestasis. METHODS:This review wil...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666180427165035
更新日期:2018-01-01 00:00:00
abstract::The possibility to treat central nervous system (CNS) disorders is strongly limited by the poor access of many therapeutic agent to the target tissues. This is mainly due to the presence of the blood-brain barrier (BBB), formed by a complex interplay of endothelial cells, astrocyte and pericytes, through which only se...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920012798356943
更新日期:2012-01-01 00:00:00
abstract::Toxicogenomics is defined as an integration of genomics (transcriptomics, proteomics and metabolomics) and toxicology. It is a scientific field that studies how the genome is involved in responses to environmental stressors and toxicants. It combines studies of mRNA expression, cell and tissue-wide protein expression ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008783884696
更新日期:2008-03-01 00:00:00
abstract::Since conventional therapeutic approaches in cancer are highly invasive they hardly prolong patient survival for more than few months. Having the ability to stimulate both cellular and humoural immune responses, immunisation with naked plasmid DNA encoding tumour-associated antigens or tumour-specific antigens has rec...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200211314030004
更新日期:2013-03-01 00:00:00
abstract::Bioavailability of orally administered drugs can be influenced by a number of factors including release from the formulation, dissolution, stability in the gastrointestinal (GI) environment, permeability through the gut wall and first-pass gut wall and hepatic metabolism. Although there are various enzymes in the gut ...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920010794328913
更新日期:2010-11-01 00:00:00
abstract::The M2 proton channel is translated by the M gene segment of influenza viruses, and has been adopted as an attractive target for influenza A viruses, on which a series of adamantane-based drugs act. However, recently epidemic influenza viruses have had strong resistant effects against the adamantane-based drugs. In th...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200215666140605130406
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Nanoparticles (NPs) are being used extensively owing to their increased surface area, targeted delivery and enhanced retention. NPs have the potential to be used in many disease conditions. Despite widespread use, their toxicity and clinical safety still remain a major concern. OBJECTIVE:The purpose of this...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200221666200103091753
更新日期:2019-01-01 00:00:00
abstract::Advances in high-throughput technologies to measure genome-scale changes of genes, proteins, and other biomolecular components ('omics') in complex biological systems have dramatically revolutionized biomedical research. However, the benefits of utilizing omics information in drug development have not yet been fully r...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008786927802
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND:Malignant tumors are the leading cause of death in humans. Due to the tedious efforts and investigations made in the field of marine drug discovery, there is now a scientific bridge between marine and pharmaceutical sciences. However, currently only few marine drugs have been lined towards anticancer directi...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200218666170221105402
更新日期:2018-01-01 00:00:00
abstract::The nature and level of systemic exposure to the active herbal constituents will profoundly affect their effects at action sites, which is fundamental in understanding their roles in the overall beneficial effects of a herbal medicine. The objective of this study is to gain a full picture of the systemic exposure to v...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200211209050494
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:Bioequivalence studies are a vital part of drug development. The average bioequivalence approach is the standard method of assessment to conclude whether the generic product is bioequivalent to the innovator product. Of late, debates are on whether the average bioequivalence approach adequately addresses dru...
journal_title:Current drug metabolism
pub_type: 杂志文章,随机对照试验
doi:10.2174/1389200221666200401105119
更新日期:2020-01-01 00:00:00
abstract::We present a review of recent investigations of anticancer drug bexarotene in this article. As one of the novel synthetic analogs of retinoids, bexarotene selectively binds to and activates the retinoid X receptor (RXRs) subfamilies, exerting a prophylactic and therapeutic effect on a large series of tumors in vitro a...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920021702160114121706
更新日期:2016-01-01 00:00:00
abstract::We report here a comprehensive evaluation of the effects of culture duration on the gene expression of P450 isoforms, uptake transporters and efflux transporters in human hepatocyte cultured in the absence and presence of the prototypical proinflammatory cytokine, interleukin-6 (IL-6). Primary collagen-matrigel sandwi...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920012802138570
更新日期:2012-09-01 00:00:00
abstract::This review focuses on identification of the important active site residues of CYP2D6 in terms of CYP2D6 polymorphism. A meta-analysis was performed on the reported literature regarding (1) values of the Michaelis-Menten constant (K(m)), maximal velocity (V(max)), and intrinsic clearance (V(max)/K(m)) for 41 metabolic...
journal_title:Current drug metabolism
pub_type: 杂志文章,meta分析,评审
doi:10.2174/138920011795495286
更新日期:2011-06-01 00:00:00
abstract::Graphene possesses a wide range of potential biomedical applications because of the unique physical and chemical properties. However, the side effects of grapheme and its derivatives on a number of biological models even on human body are still not very clear. Therefore, to properly assess the potential risk of graphe...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920021131400108
更新日期:2013-10-01 00:00:00
abstract:BACKGROUND:It is well known that ethanol can cause significant morbidity and mortality, and much of the related toxic effects can be explained by its metabolic profile. OBJECTIVE:This work performs a complete review of the metabolism of ethanol focusing on both major and minor metabolites. METHOD:An exhaustive litera...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200217666160125113806
更新日期:2016-01-01 00:00:00
abstract::Infection with the human immunodeficiency virus type 1 (HIV) results in a chronic infection that progressively cripples the host immune defenses. HIV infection is associated with increased tryptophan (trp) catabolism by the cytokine-inducible enzyme indoleamine 2,3-dioxygenase (IDO). IDO has powerful immune suppressiv...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920007780362527
更新日期:2007-04-01 00:00:00