Abstract：
:Retinoid X receptor α [RXRα; nuclear receptor (NR)2B1] is a crucial regulator in the expression of a broad array of hepatic genes under both normal and pathologic conditions. During inflammation, RXRα undergoes rapid post-translational modifications, including c-Jun N-terminal kinase (JNK)-mediated phosphorylation, which correlates with a reduction in RXRα function. A small ubiquitin-like modifier (SUMO) acceptor site was recently described in human RXRα, yet the contributors, regulators, and consequences of SUMO-RXRα are not well understood. Inflammation and other stressors alter nuclear receptor function in liver and induce SUMOylation of several NRs as part of proinflammatory gene regulation, but linkages between these two pathways in liver, or for RXRα directly, remain unexplored. We sought to determine if inflammation induces SUMOylation of RXRα in human liver-derived (HuH-7) cells. Lipopolysaccharide, interleukin-1β, and tumor necrosis factor α (TNFα) rapidly and substantially stimulated SUMOylation of RXRα. Two RXRα ligands, 9-cis retinoic acid (9cRA) and LG268, induced SUMOylation of RXRα, whereas both inflammation- and ligand-induced SUMOylation of RXRα require the K108 residue. Pretreatment with 1,9-pyrazoloanthrone (SP600125), a potent JNK inhibitor, abrogates TNFα- and 9cRA-stimulated RXRα SUMOylation. Pretreatment with SUMOylation inhibitors markedly augmented basal expression of several RXRα-regulated hepatobiliary genes. These results indicate that inflammatory signaling pathways rapidly induce SUMOylation of RXRα, adding to the repertoire of RXRα molecular species in the hepatocyte that respond to inflammation. SUMOylation, a newly described post-translational modification of RXRα, appears to contribute to the inflammation-induced reduction of RXRα-regulated gene expression in the liver that affects core hepatic functions, including hepatobiliary transport.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Schneider Aguirre R,Karpen SJdoi
10.1124/mol.113.085555subject
Has Abstractpub_date
2013-08-01 00:00:00pages
218-26issue
2eissn
0026-895Xissn
1521-0111pii
mol.113.085555journal_volume
84pub_type
杂志文章abstract：:Isoform-specific expression of endothelin-converting enzyme (ECE)-1, the major big endothelin-processing enzyme, is controlled by alternative promoters. Signaling pathways and transcriptional mechanisms of ECE-1 mRNA expression are largely unknown. To investigate ECE-1 isoform expression after protein kinase C (PKC) a...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.60.6.1332
更新日期：2001-12-01 00:00:00
abstract：:Cocaine use poses a major health problem not only because of the dependence it causes but also because of the generation of life-threatening cardiac arrhythmias following overdose. Elucidating the molecular mechanisms of action of cocaine, therefore, remains a critical step in developing treatment for cocaine addictio...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.56.6.1138
更新日期：1999-12-01 00:00:00
abstract：:In previous studies, it was shown that the overexpression of beta2-adrenoceptor (beta2AR) in the hearts of transgenic mice (Tg) leads to agonist-independent activation of adenylate cyclase and enhanced myocardial function. Here, we measured the physical coupling of beta2AR and Gs by evaluating the coimmunoprecipitatio...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.2.187
更新日期：1997-08-01 00:00:00
abstract：:The mechanism underlying the crosstalk between multiple G protein-coupled receptors remains poorly understood. We previously reported that prostaglandin E receptor EP1 facilitates dopamine D1 receptor signaling in striatal slices and promotes behavioral responses induced by D1 receptor agonists. Here, using human embr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.113.087288
更新日期：2013-09-01 00:00:00
abstract：:The growth of Plasmodium falciparum, a human malaria parasite, is sensitive to inhibition by chelators of several types. The alkylthiocarbamates and 8-hydroxyquinoline at pharmacologic doses selectively inhibit glycolysis within 6 hr in parasitized erythrocytes. The mechanism attributed to these agents is through the ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-10-01 00:00:00
abstract：:All-trans-retinoic acid (atRA) is the active metabolite of vitamin A. atRA is also used as a drug, and synthetic atRA analogs and inhibitors of retinoic acid (RA) metabolism have been developed. The hepatic clearance of atRA is mediated primarily by CYP26A1, but design of CYP26A1 inhibitors is hindered by lack of info...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.072413
更新日期：2011-08-01 00:00:00
abstract：:It has been suggested that elevated cytosolic free calcium plays a key role in acetaminophen-induced cell death. The present study has examined the effect of a toxic concentration of acetaminophen on cytosolic free calcium in single mouse hepatocytes, using the dye fura-2 and video imaging fluorescence microscopy. Cyt...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-04-01 00:00:00
abstract：:Electrical recordings were made in Xenopus oocytes to study the modulatory effects of steroids on gamma-aminobutyric acid (GABA) receptors expressed by RNA from mammalian brain and retina. GABA responses expressed by rat cerebral cortex poly(A)+ RNA were bicuculline-sensitive Cl- currents mediated by GABAA receptors. ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
abstract：:Mutations that inhibit Kv11.1 ion channel activity contribute to abnormalities of cardiac repolarization that can lead to long QT2 (LQT2) cardiac arrhythmias and sudden death. However, for most of these mutations, nothing is known about the molecular mechanism linking Kv11.1 malfunction to cardiac death. We have previ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.077966
更新日期：2012-09-01 00:00:00
abstract：:Carbachol is 100 times more potent for inhibiting cyclic AMP formation than for stimulating phosphoinositide (PI) hydrolysis in chick heart cells. To determine whether this reflects differences in agonist affinity of the receptor(s) coupled to the two responses, we measured these functional responses following removal...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-12-01 00:00:00
abstract：:Consequent to agonist exposure, many G protein-coupled receptors undergo sequestration or internalization. Results with receptors linked to adenylate cyclase, such as the beta 2-adrenergic receptor, or receptors linked to phospholipase C (PLC) have provided conflicting results regarding the role of second messenger-de...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
abstract：:The cDNA for the rat alpha 1c-adrenergic receptor (AR) has been cloned using a probe derived from the bovine alpha 1c-AR sequence. Clone rB7a has a 2.6-kilobase insert with a 1390-base pair open reading frame and encodes a receptor of 466 amino acids. The cloned receptor has 91% amino acid identity with the bovine alp...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
abstract：:The ubiquitously expressed nitric oxide (NO) receptor soluble guanylate cyclase (sGC) plays a key role in signal transduction. Binding of NO to the N-terminal prosthetic heme moiety of sGC results in approximately 200-fold activation of the enzyme and an increased conversion of GTP into the second messenger cGMP. sGC ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.036368
更新日期：2007-11-01 00:00:00
abstract：:A series of aminotriarylmethane dyes were examined for binding to the nicotinic acetylcholine receptor (AChR) from Torpedo californica. Several compounds were found to bind to the noncompetitive antagonist site of the AChR as demonstrated by inhibition of [3H]phencyclidine binding; apparent KD values ranged from 50 nM...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.55.1.159
更新日期：1999-01-01 00:00:00
abstract：:The Gαi/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression pattern...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.115.101808
更新日期：2016-04-01 00:00:00
abstract：:Anthracyclines are effective anticancer agents. However, their use is limited by cardiotoxicity, an effect linked to their ability to chelate iron and to perturb iron metabolism (Mol Pharmacol 68:261-271, 2005). These effects on iron-trafficking remain poorly understood, but they are important to decipher because trea...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.041335
更新日期：2008-03-01 00:00:00
abstract：:The thiazolidinediones are a class of antidiabetic compounds that increase the sensitivity of target tissues to insulin. An earlier study has shown that these compounds enhance the insulin-stimulated differentiation of 3T3-L1 cells and up-regulate expression of differentiation-dependent genes. We have observed that th...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
abstract：:Bufuralol 1'-hydroxylation is a prototypical reaction catalyzed by cytochrome P450 (P450) 2D6, an enzyme known to show debrisoquine/sparteine-type genetic polymorphism in humans. In the present study we further examined the roles of several human P450 enzymes, as well as P450 2D6, in the hydroxylation of (+/-)-bufural...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
abstract：:Many progestins have been developed for use in contraception, menopausal hormone therapy, and treatment of gynecological diseases. They are derived from either progesterone or testosterone, and they act by binding to the progesterone receptor (PR), a hormone-inducible transcription factor belonging to the nuclear rece...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.054312
更新日期：2009-06-01 00:00:00
abstract：:Although the thiopurine drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are well established agents for the treatment of leukemia, controversies remain regarding their main mode of action. Previous evidence has suggested that although 6-TG exerts a cytotoxic effect through incorporation of 6-thioguanine nucleot...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.1.102
更新日期：2002-07-01 00:00:00
abstract：:The tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a vascular endothelial growth factor (VEGF) receptor-2 antagonist, has been used previously either alone or in combination with chemotherapeutic drugs for treating colorectal cancer in a mouse model. We analyzed the half-life of the peptide and found that because of degradation...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.119.117234
更新日期：2019-12-01 00:00:00
abstract：:Reconstitution experiments with purified components reproduce the basic characteristics of receptor/G protein coupling, i.e., GTP-sensitive high affinity agonist binding and receptor-promoted GTP binding. However, the interaction of agonists with the A1 adenosine receptor in rat and bovine but not human brain membrane...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：:The binding affinities of 16 7-substituted 2,3-dichlorodibenzo-p-dioxins for the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cytosolic receptor protein from male Wistar rats have been determined. The EC50 value for each compound was estimated by competitive displacement of [3H]TCDD and the data illustrated that the dif...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-06-01 00:00:00
abstract：:ATP-sensitive K(+) channels are closed by the hypoglycemic sulfonylureas like glibenclamide (GBC) and activated by a class of vasorelaxant compounds, the K(+) channel openers. These channels are octamers of Kir6.x and sulfonylurea receptor (SUR) subunits with 4:4 stoichiometry. The properties of the opener-sensitive K...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1999-11-01 00:00:00
abstract：:Hepatic CYP2E1 is induced in several models of alcohol administration, but clinically relevant pathology is only observed in rats in a model involving the continuous intragastric administration of an ethanol-containing, corn oil-based, high-fat diet. The level of CYP2E1 correlates with the degree of liver pathology in...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.51.6.944
更新日期：1997-06-01 00:00:00
abstract：:Schizophrenia (SZ), schizoaffective (SZA), and bipolar (BP) disorder are neurodevelopmental psychopathological conditions related, in part, to genetic load and, in part, to environmentally induced epigenetic dysregulation of chromatin structure and function in neocortical GABAergic, glutamatergic, and monoaminergic ne...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.118.113415
更新日期：2019-01-01 00:00:00
abstract：:The epithelial sodium channel (ENaC) is believed to represent the rate-limiting step for sodium absorption in the renal collecting duct. Consequently, ENaC is a central effector affecting systemic blood volume and pressure. Sodium and water transport are dysregulated in diabetes mellitus. Peroxisome proliferator-activ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.056911
更新日期：2009-12-01 00:00:00
abstract：:Sulfation is an important pathway in the biotransformation of many drugs, xenobiotic compounds, neurotransmitters, and hormones. The sulfate donor for these reactions is 3'-phosphoadenosine-5'-phosphosulfate (PAPS). We set out to determine whether PAPS might serve as a photoaffinity ligand for sulfotransferase enzymes...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
abstract：:The competitive antagonist alpha-conotoxin-MII (alpha-CTx-MII) is highly selective for the alpha3beta2 neuronal nicotinic receptor. Other receptor subunit combinations (alpha2beta2, alpha4beta2, alpha3beta4) are >200-fold less sensitive to blockade by this toxin. Using chimeric and mutant subunits, we identified amino...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.51.2.336
更新日期：1997-02-01 00:00:00
abstract：:Thiourea, phenylthiourea, and methimazole perfused into rat liver stimulated the biliary efflux of GSSG without affecting the excretion of GSH into either the bile or the caval perfusate. The thiocarbamide moiety appears essential, since perfusion with urea, phenylurea, or N-methylimidazole did not stimulate GSSG rele...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-07-01 00:00:00
