Abstract:
BACKGROUND AND PURPOSE:5alpha,8alpha-Epidioxy-22E-ergosta-6, 22-dien-3beta-ol (ergosterol peroxide) is a major antitumour sterol produced by edible or medicinal mushrooms. However, its molecular mechanism of action has yet to be determined. Here, we examine the anticancer and anti-inflammatory effects of ergosterol peroxide. EXPERIMENTAL APPROACH:After treating RAW264.7 macrophages with LPS and purified ergosterol peroxide or ergosterol, we determined LPS-induced inflammatory cytokines, nuclear DNA binding activity of transcription factors and phosphorylation of MAP kinases (MAPKs). HT29 colorectal adenocarcinoma cells were treated with ergosterol peroxide for 5 days. To investigate the antitumour properties of ergosterol peroxide, we performed DNA microarray and RT-PCR analyses and determined the reactive oxygen species (ROS) in HT29 cells. KEY RESULTS:Ergosterol peroxide suppressed LPS-induced TNF-alpha secretion and IL-1alpha/beta expression in RAW264.7 cells. Ergosterol peroxide and ergosterol suppressed LPS-induced DNA binding activity of NF-kappaB and C/EBPbeta, and inhibited the phosphorylation of p38, JNK and ERK MAPKs. Ergosterol peroxide down-regulated the expression of low-density lipoprotein receptor (LDLR) regulated by C/EBP, and HMG-CoA reductase (HMGCR) in RAW264.7 cells. In addition, ergosterol peroxide showed cytostatic effects on HT29 cells and increased intracellular ROS. Furthermore, ergosterol peroxide induced the expression of oxidative stress-inducible genes, and the cyclin-dependent kinase inhibitor CDKN1A, and suppressed STAT1 and interferon-inducible genes. CONCLUSION AND IMPLICATION:Our results suggest that ergosterol peroxide and ergosterol suppress LPS-induced inflammatory responses through inhibition of NF-kappaB and C/EBPbeta transcriptional activity, and phosphorylation of MAPKs. Moreover, ergosterol peroxide appears to suppress cell growth and STAT1 mediated inflammatory responses by altering the redox state in HT29 cells.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Kobori M,Yoshida M,Ohnishi-Kameyama M,Shinmoto Hdoi
10.1038/sj.bjp.0706972subject
Has Abstractpub_date
2007-01-01 00:00:00pages
209-19issue
2eissn
0007-1188issn
1476-5381pii
0706972journal_volume
150pub_type
杂志文章abstract::1. Orexin-containing neurons have been implicated in feeding, sleep-wake cycles and more recently in drug-seeking behaviour. 2. Pretreatment of alcohol-preferring (iP) rats with an orexin1 receptor antagonist (SB-334867, 20 mg kg(-1), intraperitoneally) completely abolished an olfactory cue-induced reinstatement of al...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706789
更新日期:2006-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:We investigated whether or not kinin receptors play a role in diabetic blood-retinal barrier breakdown, which is a leading cause of vision loss. EXPERIMENTAL APPROACH:Blood-retinal barrier breakdown was quantified using Evans blue, and expression of kinin B(1) receptor mRNA was measured using qu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.48
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Benzofurans are newly used psychoactive substances, but their pharmacology is unknown. The aim of the present study was to pharmacologically characterize benzofurans in vitro. EXPERIMENTAL APPROACH:We assessed the effects of the benzofurans 5-APB, 5-APDB, 6-APB, 6-APDB, 4-APB, 7-APB, 5-EAPB and ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13128
更新日期:2015-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Extrahepatic vasodilation and increased intrahepatic vascular resistance represent attractive targets for the medical treatment of portal hypertension in liver cirrhosis. In both dysfunctions, dysregulation of the contraction-mediating Rho kinase plays an important role as it contributes to alter...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00158.x
更新日期:2009-05-01 00:00:00
abstract::1. Chronic benzodiazepine administration has been associated with tolerance and with downregulation of gamma-aminobutyric acidA (GABAA)-receptor binding and function. However, effects of individual benzodiazepines on brain regions have varied. 2. To compare the effects of chronic lorazepam and alprazolam, we have admi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14167.x
更新日期:1990-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The anti-cancer agent [Arg(6), D-Trp(7,9), N(me)Phe(8)]-substance P (6-11) (SP-G) modulates gastrin releasing peptide (GRP) and arginine vasopressin signalling in small cell lung cancer cells leading to growth arrest and apoptosis. We have shown that SP-G acts as a biased agonist at GRP receptors...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2008.00003.x
更新日期:2009-01-01 00:00:00
abstract::1. Vanadium compounds can mimic actions of insulin through alternative signalling pathways. The effects of three organic vanadium compounds were studied in non-ketotic, streptozotocin-diabetic rats: vanadyl acetylacetonate (VAc), vanadyl 3-ethylacetylacetonate (VEt), and bis(maltolato)oxovanadium (VM). A simple inorga...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702311
更新日期:1999-01-01 00:00:00
abstract::Anthracyclines can cause cumulative dose-related cardiotoxicity characterized by changes in Ca(2+) metabolism, including dysfunction of the sacroplasmic reticulum (SR) and decreased expression of Ca(2+)-handling proteins, such as the ryanodine receptor (RyR2). In this study, we examined the effect of dexrazoxane (ICRF...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703538
更新日期:2000-09-01 00:00:00
abstract::1. When the isolated small intestine of the rat is perfused via the mesenteric artery, an oxytocic principle (Gaddum's substance R) is released which is detectable in the perfusate after 30 min and is present in samples collected 8 h later. 2. The oxytocic activity of substance R is lost after boiling but is unaffecte...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12278.x
更新日期:1991-04-01 00:00:00
abstract::1. Ezetimibe potently inhibits the transport of cholesterol across the intestinal wall, thereby reducing plasma cholesterol in preclinical animal models of hypercholesterolemia. The effect of ezetimibe on known absorptive processes was determined in the present studies. 2. Experiments were conducted in the hamster and...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704260
更新日期:2001-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:In addition to typical GPCR kinase (GRK)-/β-arrestin-dependent internalization, dopamine D3 receptor employed an additional GRK-independent sequestration pathway. In this study, we investigated the molecular mechanism of this novel sequestration pathway. EXPERIMENTAL APPROACH:Radioligand binding...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12357
更新日期:2013-11-01 00:00:00
abstract::1 In cats anaesthetized with pentobarbitone, observations were made on respiration, spontaneous and evoked diaphragmatic electromyograms, blood pressure, heart rate, indirectly-induced contractions of the anterior tibialis muscle and nictitating membrane, and electrical excitability of the inspiratory centre in the me...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb07930.x
更新日期:1980-10-01 00:00:00
abstract::1. The uptake and release of (3)H-digitoxigenin by electrically driven, guinea-pig isolated atria (frequency 180/min) has been determined for two different medium concentrations of the genin. Both concentrations-1 x 10(-7) and 5 x 10(-7) g/ml.-caused a pronounced increase in contractile force.2. The uptake of (3)H-dig...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1968.tb08490.x
更新日期:1968-11-01 00:00:00
abstract::1. The effects of inhibiting endogenous nitric oxide (NO) synthesis with NG-monomethyl-L-arginine (L-NMMA) on the systemic and splanchnic circulation have been investigated in rats with experimental chronic portal hypertension, anaesthetized with ketamine. 2. Portal hypertension was induced by partial portal vein liga...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14233.x
更新日期:1992-01-01 00:00:00
abstract::1. Partial agonists of the beta2-adrenoceptor which activate adenylyl cyclase are widely used as bronchodilators for the relief of bronchoconstriction accompanying many disease conditions, including bronchial asthma. The bronchodilator salmeterol has both a prolonged duration of action in bronchial tissue and the abil...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701658
更新日期:1998-02-01 00:00:00
abstract::1. Hypercholesterolaemia often occurs in patients with type 2 diabetes, who therefore encounter administration of HMG-CoA reductase inhibitors. Alteration of pancreatic beta-cell function leading to an impaired insulin secretory response to glucose plays a crucial role in the pathogenesis of type 2 diabetes. Therefore...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702397
更新日期:1999-03-01 00:00:00
abstract::We have shown earlier that activation of metabotropic glutamate (mGlu) receptors using a group I-specific mGlu receptor agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG), can induce long-term depression (LTD) in the CA1 region of the hippocampus. In an attempt to determine the signal transduction mechanisms involved in ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703905
更新日期:2001-03-01 00:00:00
abstract::Forty-eight isolated rat hearts were perfused with Krebs solution and with [(3)H]-(-)-noradrenaline ([(3)H]-NA) containing 4.5 nCi/ml in 50 ng/ml, as described by Iversen (1963). To groups of six, cocaine was added to [(3)H]-NA in concentrations of 400 nM, 2 and 10 muM. To the rest Tween 80, 25 mug/ml was added to [(3...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb10686.x
更新日期:1974-07-01 00:00:00
abstract::1. The responses of rat isolated aortae to vasoconstrictor and vasodilator agents have been studied in 14-day streptozotocin-diabetic rats. The effects of treatment with the aldose reductase inhibitor, ponalrestat, on these responses have also been investigated. 2. Maximum contractile responses and aortic sensitivity ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17028.x
更新日期:1994-10-01 00:00:00
abstract::1. Calcium entry via neuronal calcium channels is essential for the process of neurotransmission. We investigated the calcium channel subtypes involved in the operation of cardiac autonomic neurotransmission by examining the effects of selective calcium channel blockers on the inotropic responses to electrical field s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702629
更新日期:1999-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Glucocorticoids appear to control Na⁺ absorption in pulmonary epithelial cells via a mechanism dependent upon serum and glucocorticoid-inducible kinase 1 (SGK1), a kinase that allows control over the surface abundance of epithelial Na⁺ channel subunits (α-, β- and γ-ENaC). However, not all data s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.01860.x
更新日期:2012-06-01 00:00:00
abstract::Free radicals as well as the AT1 receptor are involved in the pathogenesis of cardiovascular disease. Both the intracellular mechanisms of AT1 receptor regulation and the effect of free radicals on AT1 receptor expression are currently unknown. This study investigates the role of free radicals in the modulation of AT1...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703623
更新日期:2000-10-01 00:00:00
abstract::1. Electroconvulsive treatment (ECT) of rabbits produced ocular inflammation consisting of conjunctival hyperaemia, miosis and protein extravasation into the aqueous humour, reflected by the so-called aqueous flare response (AFR): the maximal reduction in pupil size was 3.8 +/- 0.1 mm (s.e. of mean, n = 16) while the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701083
更新日期:1997-04-01 00:00:00
abstract::1. The potencies of some beta-adrenoreceptor blocking drugs in reducing noradrenaline uptake by the isolated heart were compared with their potencies in reducing the release of noradrenaline from the heart by tyramine.2. Of the drugs tested, propranolol, pronethalol and dichloroisoprenaline were the most potent in blo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1968.tb07957.x
更新日期:1968-09-01 00:00:00
abstract:BACKGROUND & PURPOSE:The therapeutically available quinolone antibiotic moxifloxacin has been used as a positive control for prolonging the QT interval in both clinical and non-clinical studies designed to assess the potential of new drugs to delay cardiac repolarization. Despite moxifloxacin prolonging QT, it has not ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706900
更新日期:2006-12-01 00:00:00
abstract::Hind paw oedema in rats, measured by plethysmography or extravasation of Evans Blue dye into the skin, after subplantar injection of submaximal doses of carrageenin (1-100 micrograms) was significantly increased for 4 h during kininase II inhibition with captopril (1 mg kg-1, s.c.). Submaximal oedema, as assessed by p...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb16435.x
更新日期:1984-05-01 00:00:00
abstract::The peptides, neurotensin, substance P, somatostatin, and bombesin, several analogues and fragments of neurotensin and compound 48/80, all caused the secretion of both endogenous 5-hydroxytryptamine (5-HT) and histamine. There was no differential effect of any of the secretagogues tested on the secretion of 5-HT and h...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10069.x
更新日期:1984-02-01 00:00:00
abstract::1 The effect of compound 48/80 was studied on the twitch-like contractions of the longitudinal muscle of guinea-pig ileum induced by electrical stimulation of intramural cholinergic nerves. 2 Compound 48/80 alone, at concentrations up to 30 microgram/ml, had no effect on the twitch contractions. The contraction to exo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb17312.x
更新日期:1978-12-01 00:00:00
abstract::1. The experiment investigated the effects of psychotropic drugs on enzymes in vitro.2. Chlorpromazine inhibits mitochondrial malate dehydrogenase in concentrations of 1.4x10(-4)M and above. No effect was observed below this concentration.3. A sharp inflection in the [unk]/drug plot was also seen with chlorpromazine (...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb10582.x
更新日期:1969-10-01 00:00:00
abstract::1. Arachidonic acid caused larger contractions to indomethacin-tested guinea-pig trachea than in control tracheae. 2. No change in contractions was obtained in tracheae treated with 5,8, 11, 14, eicosatetraynoic acid (ETYA 10 micro M). 3. ETYA (100 micro M) blocked the effect of indomethacin on arachidonic acid-induce...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09250.x
更新日期:1982-08-01 00:00:00