Abstract：
:Nod2 is an intracellular pattern recognition receptor that detects a conserved moiety of bacterial peptidoglycan and subsequently activates proinflammatory signaling pathways. Mutations in Nod2 have been implicated to be linked to inflammatory granulomatous disorders, such as Crohn's disease and Blau syndrome. Many phytochemicals possess anti-inflammatory properties. However, it is not known whether any of these phytochemicals might modulate Nod2-mediated immune responses and thus might be of therapeutic value for the intervention of these inflammatory diseases. In this report, we demonstrate that curcumin, a polyphenol found in the plant Curcuma longa, and parthenolide, a sesquiterpene lactone, suppress both ligand-induced and lauric acid-induced Nod2 signaling, leading to the suppression of nuclear factor-kappaB activation and target gene interleukin-8 expression. We provide molecular and biochemical evidence that the suppression is mediated through the inhibition of Nod2 oligomerization and subsequent inhibition of downstream signaling. These results demonstrate for the first time that curcumin and parthenolide can directly inhibit Nod2-mediated signaling pathways at the receptor level and suggest that Nod2-mediated inflammatory responses can be modulated by these phytochemicals. It remains to be determined whether these phytochemicals possess protective or therapeutic efficacy against Nod2-mediated inflammatory disorders.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Huang S,Zhao L,Kim K,Lee DS,Hwang DHdoi
10.1124/mol.108.046169subject
Has Abstractpub_date
2008-07-01 00:00:00pages
274-81issue
1eissn
0026-895Xissn
1521-0111pii
mol.108.046169journal_volume
74pub_type
杂志文章abstract：:To enable the detailed pharmacological characterization of five bombesin (BN) analogs with respect to the human gastrin-releasing peptide (GRP) receptor, we ectopically expressed the receptor in BALB/3T3 cells. In such cells (termed GR1 cells), GRP stimulated DNA synthesis and Ca2+ mobilization. Two of these analogs, ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:By limiting unrestricted activation of intracellular effectors, compartmentalised signalling of cyclic nucleotides confers specificity to extracellular stimuli and is critical for the development and health of cells and organisms. Dissecting the molecular mechanisms that allow local control of cyclic nucleotide signal...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.119.118869
更新日期：2020-02-28 00:00:00
abstract：:Differential display reverse transcription-polymerase chain reaction was used to identify mRNAs that are differentially expressed in the brain of rats treated chronically with the reference tricyclic antidepressant, imipramine, in comparison with control rats. The gene encoding for a mutation suppressor for Sec4-8 yea...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.6.1332
更新日期：2002-12-01 00:00:00
abstract：:Current evidence suggests that DNA fragmentation plays an integral role in mediating cytotoxicity that results from thymidine nucleotide depletion ("thymineless death"). Recently, Ayusawa et al. [Mutat. Res. 200:221-230 (1988)] reported that dTMP starvation induces cellular processes that result in the release of 50-2...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
abstract：:Trypanosoma brucei encodes a relatively high number of genes of the equilibrative nucleoside transporter (ENT) family. We report here the cloning and in-depth characterization of one T. brucei brucei ENT member, TbNT9/AT-D. This transporter was expressed in Saccharomyces cerevisiae and displayed a uniquely high affini...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.106.031559
更新日期：2007-03-01 00:00:00
abstract：:We cloned and expressed a human metabotropic glutamate receptor 1 alpha (HmGluR1 alpha) in a novel cell line. The human mGluR1 alpha cDNA was found to be 86% identical to rat mGluR1 alpha, and the predicted protein sequence was found to be 93% identical to rat mGluR1 alpha. We expressed HmGluR1 alpha in AV12-664, an a...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-10-01 00:00:00
abstract：:Depending on their primary structure, the 28 mammalian transient receptor potential (TRP) cation channels identified so far can be sorted into 6 subfamilies: TRPC ("Canonical"), TRPV ("Vanilloid"), TRPM ("Melastatin"), TRPP ("Polycystin"), TRPML ("Mucolipin"), and TRPA ("Ankyrin"). The TRPV subfamily (vanilloid recept...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.109.055624
更新日期：2009-06-01 00:00:00
abstract：:Activation of endothelial nitric-oxide synthase (eNOS) has been shown to occur through various pathways involving increases in the cytosolic Ca(2+) concentration, activation of the phosphatidylinositol-3' kinase/Akt pathway, as well as regulation by other kinases and by protein-protein interactions. We have recently r...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.63.4.886
更新日期：2003-04-01 00:00:00
abstract：:Matrix metalloproteinases (MMPs) are synthesized in response to diverse stimuli, including cytokines, growth factors, hormones, and oxidative stress. Here we show that the nitric oxide (NO) donor 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA-NO) and NO from murine macrophages transcriptionally regulate MMP-13 expressi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.4.927
更新日期：2002-10-01 00:00:00
abstract：:In the rat isolated optic nerve, nitric oxide (NO) activates soluble guanylyl cyclase (sGC), resulting in a selective accumulation of cGMP in the axons. The axons are also selectively vulnerable to NO toxicity. The experiments initially aimed to determine any causative link between these two effects. It was shown, usi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.1.97
更新日期：2002-01-01 00:00:00
abstract：:The beta 3-adrenergic receptor (beta 3AR) is a member of the super-family of G protein-coupled receptors that are characterized by seven putative transmembrane helices connected by hydrophilic loops. The mechanism by which the activated beta ARs transmit the signals across the plasma membrane involves the stimulation ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:To study the molecular pharmacology of low-voltage-activated calcium channels in biophysical detail, human medullary thyroid carcinoma (hMTC) cells were investigated using the single-channel technique. These cells had been reported to express T-type whole-cell currents and a Ca(v)3.2 (or alpha 1H) channel subunit. We ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.3.682
更新日期：2002-03-01 00:00:00
abstract：:The effect of halothane on synthesis of retained and secreted proteins was investigated using isolated perfused rat livers. Anesthetic exposure rapidly inhibited synthesis of total liver proteins in a dose-dependent manner by a mechanism which appeared to involve reduced rates of both peptide chain initiation and elon...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-09-01 00:00:00
abstract：:Multidrug resistance-associated protein 2 (MRP2) transports glutathione conjugates, glucuronide conjugates, and sulfated conjugates of bile acids. In the present study, we examined the role of charged amino acids in the transmembrane domains of rat Mrp2, conserved among MRP families, using the isolated membrane vesicl...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.5.1077
更新日期：2001-05-01 00:00:00
abstract：:Inhibition of cathepsin C, a dipeptidyl peptidase that activates many serine proteases, represents an attractive therapeutic strategy for inflammatory diseases with a high neutrophil burden. We recently showed the feasibility of blocking the activation of neutrophil elastase, cathepsin G, and proteinase-3 with a singl...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.045682
更新日期：2008-06-01 00:00:00
abstract：:Bryostatin 1 and phorbol-12-myristate-13-acetate (PMA) are both potent activators of protein kinase C (PKC), although in primary mouse keratinocytes bryostatin 1 does not induce differentiation and blocks PMA-induced differentiation. We report here that in primary mouse keratinocytes PMA caused translocation of PKC-ep...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：:At central excitatory synapses, the transient elevation of intracellular calcium reduces N-methyl-D-aspartate (NMDA) receptor activity. Such 'calcium-dependent inactivation' is mediated by interactions of calcium/calmodulin and alpha-actinin with the C terminus of NMDA receptor 1 (NR1) subunit. However, inactivation i...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.3.595
更新日期：2002-03-01 00:00:00
abstract：:Ca2-dependent protein phosphorylations activated by calmodulin or phospholipid were studied using selective inhibitors. Both protein phosphorylations were inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and its derivatives. Kinetic analysis indicated that the primary effect of these agents was me...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-09-01 00:00:00
abstract：:The hexapeptide [pGlu6,Pro9]substance P (SP)6-11, septide, has been shown to be an agonist as potent as SP in eliciting smooth muscle contraction in several in vitro preparations, while being a poor competitor of labeled SP binding. These results, as well as other pharmacological data, have suggested the existence of ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-02-01 00:00:00
abstract：:The expression and molecular regulation of the cytochrome P450IA (P450IA) gene subfamily have been examined in rat hepatic tissue after treatment with pyridine. The microsomal ethoxyresorufin O-deethylase activity, which has been shown to be specific for the P450IA subfamily, was increased approximately 2- and 3.5-fol...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-07-01 00:00:00
abstract：:We have synthesized and characterized a high-affinity alpha 1-adrenergic receptor probe, 4-amino-6,7-dimethoxy-2[4'- [5"(3"'-125I-iodo-4"'-aminophenyl)pentanoyl]-1'-piperazinyl] quinazoline (125I-A55453). This ligand binds reversibly to rat hepatic plasma membranes with high affinity (KD = 77 +/- 6 pM), and it labels ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-09-01 00:00:00
abstract：:Guanine nucleotide-binding proteins (G proteins) transduce signals from agonist- and light-sensitive receptors. In the visual excitation system, the photon receptor rhodopsin is coupled to the G protein Gt (transducin). Gt is composed of alpha, beta, and gamma subunits; the alpha subunit binds guanine nucleotide, wher...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-06-01 00:00:00
abstract：:Cannabinoids have been implicated in the reduction of glioma growth. The present study investigated a possible relationship between the recently shown induction of cyclooxygenase (COX)-2 expression by the endocannabinoid analog R(+)methanandamide [R(+)-MA] and its effect on the viability of H4 human neuroglioma cells....
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.002618
更新日期：2004-12-01 00:00:00
abstract：:We have reported previously that the transmembrane domains of the cholecystokinin-B/gastrin receptor (CCK-BR) comprise a putative ligand binding pocket. In the present study, we examined whether amino acid substitutions within the CCK-BR pocket altered the affinities and/or functional activities of L-365,260 (the prot...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.54.5.857
更新日期：1998-11-01 00:00:00
abstract：:Supplemental oxygen therapy is frequently used in the treatment of pulmonary insufficiency, as is encountered in premature infants, and in patients with acute respiratory distress syndrome. However, hyperoxia causes lung damage in experimental animals and may do so in humans. Cytochrome P4501A enzymes have been implic...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.3.507
更新日期：2002-03-01 00:00:00
abstract：:CC and CXC chemokines coinduced in fibroblasts and leukocytes by cytokines and microbial agents determine the number of phagocytes infiltrating into inflamed tissues. Interleukin-8/CXCL8 and stromal cell-derived factor-1/CXCL12 significantly and dose-dependently increased the migration of monocytes, expressing the cor...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.045146
更新日期：2008-08-01 00:00:00
abstract：:Expression vectors were designed and constructed to achieve optimum production of two different isozymes of rat glutathione S-transferase (GST) (EC 2.5.1.18) in COS cells, for studies of drug resistance. Promoter-enhancer elements from the simian virus 40 (SV40) early-region or the mouse alpha 2(I)-collagen gene, GST ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-04-01 00:00:00
abstract：:The L-type amino acid transporter 1 (LAT1) is an Na(+)-independent neutral amino acid transporter subserving the amino acid transport system L. Because of its broad substrate selectivity, system L has been proposed to be responsible for the permeation of amino acid-related drugs through the plasma membrane. To underst...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.4.729
更新日期：2002-04-01 00:00:00
abstract：:The effect of mercuric acetate on the activities of deoxyuridine triphosphate nucleotidohydrolase (dUTPase), DNA polymerase (alpha, beta), and uracil-DNA glycosylase has been studied in cultured human KB cells. There was a dose- and time-dependent inactivation of both dUTPase and DNA polymerase alpha activities by mer...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-02-01 00:00:00
abstract：:The mechanisms underlying mastoparan-induced elevation of the intracellular free calcium concentration ([Ca2+]i) were investigated in the insulin-secreting cell lines RINm5F and HIT. In both cell types, micromolar concentrations of mastoparan induced a prompt increase of [Ca2+]i, measured as an increase in fura-2 fluo...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
