Abstract：
:Endoplasmic reticulum (ER) stress and associated protein aggregation are closely associated with human diseases, including alterations in hepatic lipid metabolism. Inhibition of ER stress can have a significant effect on the prevention of hepatic dyslipidemia. Here, we studied the role of 4-phenylbutyric acid (4-PBA), a chemical chaperone, on ER stress-induced hepatic lipid accumulation. We studied ER stress induction following CCl4 exposure and delineated mechanisms of the CCl4-induced ER stress response in liver tissue from mice. CCl4 affected the formation of disulfide bonds through excessive hyper-oxidation of protein disulfide isomerase (PDI). Increased complex formation between PDI and its client proteins persisted in CCl4-exposed samples. Conversely, 4-PBA inhibited ER stress via secretion of apolipoprotein B and prevention of hepatic lipid accumulation. We also studied the mechanism-based pharmacokinetic and pharmacodynamic profiles and identified the ER stress-related proteins GRP78 and CHOP, along with plasma apolipoprotein B and triglyceride levels, as novel biomarkers of ER stress-induced hepatic lipid accumulation. ER stress and its clinical relevance for therapeutic approaches were well correlated with the activity of the ER stress regulator 4-PBA, which may be a promising drug candidate for the treatment of hepatic lipid accumulation, such as hepatic steatosis.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Lee HY,Marahatta A,Bhandary B,Kim HR,Chae HJdoi
10.1016/j.ejphar.2016.02.068subject
Has Abstractpub_date
2016-04-15 00:00:00pages
104-12eissn
0014-2999issn
1879-0712pii
S0014-2999(16)30111-Xjournal_volume
777pub_type
杂志文章abstract：:Multidrug resistance phenotype in mammalian cells is often correlated with overexpression of P-glycoprotein or Multidrug Resistance-Associated protein (MRP(1)). Both proteins are energy-dependent drug efflux pumps that efficiently reduce the intracellular accumulation and hence the cytotoxicity of many natural cytotox...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00047-9
更新日期：2000-03-17 00:00:00
abstract：:Kynuramine increased heart rate and blood pressure in pithed rats. Heart rate responses were blocked by beta-adrenoceptor antagonists and reserpine pretreatment. Both of these treatments reduced the pressor responses to kynuramine. Remaining pressor activity was inhibited by phentolamine. The pressor responses to kynu...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90346-1
更新日期：1983-02-18 00:00:00
abstract：:The study concerned the effect of arachidonic acid metabolites on the inflammatory reaction in granulation tissue of open wounds in rats. Metabolites or inhibitors were applied in a wound chamber attached to circular, open, full-thickness skin wounds 5 days post-wounding. The adjacent wound served as control. Blood fl...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90454-0
更新日期：1984-01-27 00:00:00
abstract：:The study concerned the effects of chlorpromazine (CPZ), monodesmethyl-chlorpromazine (NOR1-CPZ), didesmethyl-chlorpromazine (NOR2-CPZ), and chlorpromazine-N-oxide (CPZ-NO) on the EEG and on dopamine metabolism of the isolated perfused rat brain. Isolated brains were perfused with 100 ml of a perfusion medium containi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(79)90267-x
更新日期：1979-07-01 00:00:00
abstract：:Kakkon-to is composed of seven medicinal herbs and exhibited novel antipyretic activity by suppressing interleukin-1alpha production responsive to interferon in a murine intranasal influenza virus infection model. Using this model, antipyretic compounds with such novel biological activities were characterized from the...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00121-6
更新日期：1998-05-01 00:00:00
abstract：:Right ventricular papillary muscles of the guinea-pig heart were electrically stimulated. Cromakalim 10-100 microM and Ro 31-6930 3 microM depressed the contractile force and shortened the duration of action potentials. Glibenclamide 0.3-3 microM, ATP 100 microM and alpha, beta-methylene ATP (alpha, beta-meATP) 30 mic...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90244-x
更新日期：1992-03-17 00:00:00
abstract：:The inhibition by various serotonin agonists and antagonists of the binding of 3 nM 3H-d-LSD, 1.7 nM 3H-serotonin and 0.22 nM 3H-spiperone to homogenates of calf hippocampus and frontal cortex was studied. The 50% inhibitory concentration (IC50) for these drugs versus 3H-d-LSD binding had similar values to and correla...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(80)90141-7
更新日期：1980-08-29 00:00:00
abstract：:Modafinil [2-((diphenylmethyl) sulfinyl) acetamide] is a central nervous system stimulant. It has received considerable attention as a potential psychotropic agent in several psychiatric disorders. The current study was carried out to investigate the effect of modafinil after acute administration on animal models of p...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.04.035
更新日期：2014-08-05 00:00:00
abstract：:Vasopressin ([Arg(8)]vasopressin)-induced contraction was characterized using receptor agonists and antagonists for vasopressin and channel blockers in the rat basilar artery ring preparations. Vasopressin induced rhythmic contractions superimposed on a contraction in endothelium-intact preparations but not in denuded...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)00781-6
更新日期：2001-03-23 00:00:00
abstract：:To investigate cellular electrophysiologic alterations due to lipid peroxidation of the cell membrane by free radicals as a possible cause of coronary reperfusion arrhythmias, we studied the effects of t-butyl hydroperoxide on the spontaneous action potential and membrane currents of the rabbit sinoatrial and atrioven...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(95)90027-6
更新日期：1995-03-16 00:00:00
abstract：:Substance-related and addictive disorders (SRADs) are characterized by compulsive drug use and recurrent relapse. The persistence of pathological drug-related memories indisputably contributes to a high propensity to relapse. Hence, strategies to disrupt reconsolidation of drug reward memory are currently being pursue...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2021.173911
更新日期：2021-01-24 00:00:00
abstract：:Neuroinflammation contributes to the pathogenesis of neurological disorders including stroke, head trauma, multiple sclerosis, amyotrophic lateral sclerosis as well as age-associated neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Therefore, anti-inflammatory drugs could be used to slow the...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.11.038
更新日期：2012-02-15 00:00:00
abstract：:Ischemia/reperfusion injury ends up in the cascade of excitotoxic stimulation of superoxide and nitric oxide formation leading to the generation of highly reactive products, including peroxinitrite and hydroxyl radical, which are capable of damaging lipids, proteins and DNA. Several polyphenolic compounds scavenge the...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.09.038
更新日期：2010-01-25 00:00:00
abstract：:The aim of the research was to characterize muscarinic receptors of bovine ciliary muscle and to investigate the desensitization process. The role of protein kinase C was analyzed. The results show that muscarinic receptors of bovine ciliary muscle have the pharmacological characteristics of the M3 subtype. Acute expo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)10122-4
更新日期：1997-07-09 00:00:00
abstract：:Acute noise stress decreased [3H]5-hydroxytryptamine ([3H]5-HT) uptake in synaptosomes from rat hypothalamus, hippocampus and cerebral cortex. The decrease was due to the maximum rate of [3H]5-HT uptake, which peaked 30 min after stress and partly returned to resting values within 4 h, with no changes in affinity (Km ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90211-y
更新日期：1993-09-14 00:00:00
abstract：:Endothelium-dependent contraction elicited by high concentrations of acetylcholine was described in hypertensive as well as in aged normotensive rats. The contribution of endothelium-derived constricting factor (EDCF) to norepinephrine-induced contraction is still unknown. We aimed to compare EDCF participation to nor...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.05.031
更新日期：2011-09-30 00:00:00
abstract：:Barbiturates derived by minor structural changes to the butenyl sidechain of the convulsant 5-ethyl-5-(3'-methyl-but-2'-enyl)-barbituric acid are almost devoid of convulsant activity, but all have anaesthetic and anticonvulsant effects. Anticonvulsant activity is also observed in the convulsant barbiturate. Increased ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(79)90382-0
更新日期：1979-04-15 00:00:00
abstract：:Guanosine 3',5'-cyclic monophosphate (cGMP) is an important second messenger in many biological systems including vascular smooth muscle where it mediates relaxation. Cellular levels of cGMP are regulated primarily by three enzymes; nitric oxide (NO) synthase, soluble guanylate cyclase, and cGMP-phosphodiesterase. Bas...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00307-0
更新日期：1998-06-19 00:00:00
abstract：:Alopecia is resulted from various factors that can decrease the regeneration capability of hair follicles and affect hair cycles. This process can be devastating physically and psychologically. Nevertheless, the available treatment strategies are limited, and the therapeutic outcomes are not satisfactory. According to...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2020.173197
更新日期：2020-08-15 00:00:00
abstract：:An 8-arm radial maze task was used to assess the possible role of the opiate system in the spatial memory of the rat. Increasing doses of etonitazene (0.005-0.06 mg/kg i.p.) and morphine (2.5-100 mg/kg i.p.) significantly impaired performance in the working memory components of the task. For both drugs this impairment...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90811-7
更新日期：1994-12-27 00:00:00
abstract：:We studied the interaction of S-methylisothiourea (a selective inducible nitric oxide synthase inhibitor) with rofecoxib (a selective cyclooxygenase-2 inhibitor) and mefenamic acid (a non-selective cyclooxygenase inhibitor) in adjuvant-induced arthritis in female albino Wistar rats, applying the isobolographic analysi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.10.047
更新日期：2007-02-05 00:00:00
abstract：:We examined the effects of the administration of 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-pregna-1,4,9( 11)-triene-3,20-dione, monomethansulfonate (U74389F), a 21-aminosteroid and so-called lazaroid, that is characterized by an inhibitory activity against iron-dependent lipid peroxidation, on ischemi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00638-9
更新日期：1995-12-29 00:00:00
abstract：:The investigation examined the mechanism of the increase in brain tryptophan concentration of rats treated with d-amphetamine. Certain well recognised influences upon brain tryptophan have been excluded as responsible. Thus, the effect is not associated with changes in the plasma concentrations of NEFA or free tryptop...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90307-2
更新日期：1978-06-15 00:00:00
abstract：:We investigated the influence of inhibition of nitric oxide (NO) synthase, using NG-nitro-L-arginine (L-NNA) or NG-mono-methyl-L-arginine (L-NMMA), and the effects of exogenous donor of NO, such as glyceryl trinitrate (GTN), on the healing of chronic gastric ulcers induced by acetic acid, on gastric blood flow around ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90997-v
更新日期：1993-08-03 00:00:00
abstract：:The 5-lipoxygenase inhibitors WY-50,295 tromethamine, A-64,077, L-663,536 and ICI-207,968 were compared in a reverse passive Arthus reaction-induced pleurisy model of eicosanoid biosynthesis in the rat. When a 1 h pretreatment schedule was employed, all four inhibitors equivalently blocked leukotriene B4 (LTB4) produc...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90196-w
更新日期：1991-01-25 00:00:00
abstract：:In conscious normotensive cats intraventricular (i.c.v.) administration of histamine (2.0-50.0 mug) induced dose-related rises in blood pressure, with no increase in heart rate. The hypertensive response elicited by a sub-maximal dose of histamine (10.0 mu i.c.v.) was significantly antagonised by central pretreatment ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(76)90284-3
更新日期：1976-03-01 00:00:00
abstract：:Effects of the alpha2-adrenoceptor antagonist yohimbine on the antinociception produced by a low dose of naloxone were examined in a rat model of carrageenan-induced inflammation. In rats receiving saline prior to naloxone injection, the low dose of naloxone (5 microg/kg, i.p.) significantly prolonged paw withdrawal l...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00151-4
更新日期：1998-05-08 00:00:00
abstract：:The cyclic peptide urotensin II has recently been cloned from human and reported to potently constrict primate blood vessels. To elucidate the cellular signalling mechanisms of this peptide, we investigated a possible relationship of vasomotor effects of human urotensin II and phosphoinositide turnover in isolated rab...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00672-5
更新日期：2000-10-13 00:00:00
abstract：:It has been well documented that nordihydroguaiaretic acid (NDGA), a phenolic lignan isolated from the creosote bush, Larrea tridentate, has anti-cancer activity in vitro and in vivo. Several mechanisms have been identified that could contribute to these actions, as NDGA directly inhibits metabolic enzymes and recepto...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.06.012
更新日期：2009-08-15 00:00:00
abstract：:Specific binding of [3H]imipramine to its recognition sites in frontal cortex and levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) as well as uptake of serotonin by crude synaptosomal (P2) fraction were determined in a group of rats chronically (for 21 days) treated with differen...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90429-8
更新日期：1987-06-19 00:00:00
