Abstract:
:In the present study, a novel synthetic compound 4-(2-(cyclohex-2-enylidene)hydrazinyl)quinolin-2(1H)-one (CYL-4d) was found to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production without affecting cell viability or enzyme activity of expressed inducible NO synthase (iNOS) in RAW 264.7 macrophages. CYL-4d exhibited parallel inhibition of LPS-induced expression of iNOS protein, iNOS mRNA and iNOS promoter activity in the same concentration range. LPS-induced activator protein-1 (AP-1) DNA binding, AP-1-dependent reporter gene activity and c-Jun nuclear translocation were all markedly inhibited by CYL-4d with similar efficacy, whereas CYL-4d produced a weak inhibition of nuclear factor-kappaB (NF-kappaB) DNA binding, NF-kappaB-dependent reporter gene activity and p65 nuclear translocation without affecting inhibitory factor-kappa B alpha (I kappa B alpha) degradation. CYL-4d had no effect on the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and its upstream activator MAPK kinase (MEK) 3, whereas it significantly attenuated the phosphorylation of c-Jun, c-Jun NH(2)-terminal kinase (JNK) and its upstream activator MEK4 in a parallel concentration-dependent manner. Other Toll-like receptors (TLRs) ligands (peptidoglycans, double-stranded RNA, and oligonucleotide containing unmethylated CpG motifs)-induced iNOS protein expression were also inhibited by CYL-4d. Furthermore, the NO production from BV-2 microglial cells as well as rat alveolar macrophages in response to LPS was diminished by CYL-4d. These results indicate that the blockade of NO production by CYL-4d in LPS-stimulated RAW 264.7 cells is attributed mainly to interference in the MEK4-JNK-AP-1 signaling pathway. CYL-4d inhibition of NO production is not restricted to TLR4 activation and immortalized macrophage-like cells.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Lin MW,Tsao LT,Chang LC,Chen YL,Huang LJ,Kuo SC,Tzeng CC,Lee MR,Wang JPdoi
10.1016/j.bcp.2007.02.009subject
Has Abstractpub_date
2007-06-01 00:00:00pages
1796-806issue
11eissn
0006-2952issn
1873-2968pii
S0006-2952(07)00126-8journal_volume
73pub_type
杂志文章abstract::3-alpha-Methyl substituted digitoxigenin-3-beta-glucoside (methyl-dtg-gluc) displays unusual features, e.g. a high dissociation rate constant from its binding site leading to rapid reversibility of the inotropic and toxic effects, and a flat dose-response curve attaining higher inotropic maxima thus indicating an incr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90059-4
更新日期:1982-08-01 00:00:00
abstract::Phospholipase A2 (PLA2) cleave phospholipids preferentially at the sn-2 position, liberating free fatty acids and lysophospholipids. They are classified into six main groups based on size, location, function, substrate specificity and calcium requirement. These classes include secretory PLA2 (sPLA2), cytosolic (cPLA2)...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2014.05.022
更新日期:2014-08-15 00:00:00
abstract::The distribution of renal adenosine A(1) receptors was investigated in rats with glycerol- or mercuric chloride (HgCl(2))-induced acute renal failure. Receptors were localised by autoradiography using [(3)H]8-cyclopentyl-1,3-dipropylxanthine ([(3)H]DPCPX), a selective A(1) adenosine receptor antagonist. In saline-inje...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00369-x
更新日期:2000-03-15 00:00:00
abstract::The effects of muscimol, aminooxyacetic acid (AOAA), diamino-n-butyric acid (DABA), baclofen, bicuculline, picrotoxin, strychnine, diazepam, phenobarbitone and phenytoin on cimetidine-induced seizures were studied in mice. Cimetidine (400-1000 mg/kg, i.p.) induced dose-dependent tonic convulsion. Muscimol, AOAA and DA...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90606-w
更新日期:1993-12-14 00:00:00
abstract::The differentiation-inducing factor-1 (DIF-1) is a lipophilic signal molecule (chlorinated alkylphenone) that induces stalk-cell differentiation in the cellular slime mould Dictyostelium discoideum. It has also been shown that DIF-1 and its derivative (DIF-3) suppress cell growth in mammalian tumor cells. In the prese...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2005.06.002
更新日期:2005-09-01 00:00:00
abstract::The aim of this review is to summarize current available information about the role of PI3K/AKT/mTOR signaling in head and neck cancer as a potential target for new therapy options. 90% of all head and neck cancers are squamous cell carcinomas (HNSCC). The most common genetic alteration is inactivation of p16 gene whi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2019.113729
更新日期:2020-02-01 00:00:00
abstract::Drug-specific antibody fragments can enhance the elimination of some drugs by redistributing drug from tissues into serum and allowing renal excretion of the drug-antibody complex. This approach could potentially be used to enhance the elimination of compounds such as polychlorinated biphenyls that have very long elim...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90055-8
更新日期:1994-08-17 00:00:00
abstract::Epoxyeicosatrienoic acids (EETs), a family of cytochrome P450 epoxygenase metabolites of arachidonic acid, are believed to have an autocrine or paracrine role in the regulation of neurons or neuroendocrine cells. The effects of 14,15-EET on ionic currents were investigated in rat pituitary GH(3) cells. In the whole-ce...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00317-8
更新日期:2000-07-15 00:00:00
abstract::Gemcitabine (dFdC) is a new cytidine analogue which is active mainly by the incorporation of its triphosphate (dFdCTP) into DNA, leading to cell death. We determined incorporation of dFdC into nucleic acids of two solid tumour cell lines: the murine colon carcinoma cell line Colon 26-10, the human ovarian carcinoma ce...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90566-f
更新日期:1993-08-17 00:00:00
abstract::When rat peritoneal leucocytes were incubated with carbon tetrachloride, a PLA2 was activated, eicosanoids were generated and lysosomal and cytoplasmic enzymes were released. The predominant eicosanoid generated was TXB2 with lesser amounts of PGE2, 6-keto PGF1 alpha and LTB4. Preincubation of the cells with two struc...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90693-8
更新日期:1985-05-01 00:00:00
abstract::The constitutive androstane receptor (CAR) modulates the transcription of numerous genes involving drug metabolism, energy homeostasis, and cell proliferation. Most functions of CAR however were defined from animal studies. Given the known species difference of CAR and the significant cross-talk between CAR and the pr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.08.087
更新日期:2015-11-01 00:00:00
abstract::Sepsis is an etiologically complex and often fatal inflammatory process involving a multitude of cytokine signaling pathways. Tumor necrosis factor α (TNFα) acts as a central regulator of the acute-phase inflammatory response by recruiting immune cells, including circulating monocyte/macrophages, to sites of infection...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.11.017
更新日期:2019-01-01 00:00:00
abstract::Nucleoside diphosphokinase (NDK) of human platelets has been purified by chromatography on Blue Sepharose CL-6B gel (purification factor of 950) and shown to be free of adenylate kinase, ATPase and adenylate cyclase. The molecular weight was 70,000 with subunits of 17,000. The pH optimum was 8.0 Km values for ATP and ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90762-8
更新日期:1986-12-15 00:00:00
abstract::P-glycoprotein (P-gp) plays critical roles in mediating the cytotoxicity of many drugs that are P-gp substrates. Previously, we reported that P-glycoprotein (P-gp) is the foremost efflux transporter of deoxynivalenol (DON), which is one of the most abundant mycotoxins. However, whether DON changes the expression of P-...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.08.020
更新日期:2018-10-01 00:00:00
abstract::Cardiorenal syndrome type-3 (CRS-3) is characterized by acute cardiac injury induced by acute kidney injury. Here, we investigated the causes of CRS-3 by analyzing cardiac function after renal ischemia-reperfusion injury (IRI) using echocardiography and evaluation of pro-inflammatory markers, calcium balance, mitochon...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.113832
更新日期:2020-04-01 00:00:00
abstract::Approximately 60% of the total particulate phosphodiesterase activity occurring in cardiac tissue was associated with the nuclear fraction. Cyclic GMP phosphodiesterase activity of the purified cardiac nuclear fraction was selectively inhibited by trifluoperazine (I50 = 19 microM) with negligible inhibition (less than...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90447-6
更新日期:1982-03-01 00:00:00
abstract::The genetically controlled polymorphic oxidation of debrisoquine and sparteine is caused by the absence or functional deficiency of a cytochrome P-450 isozyme. In order to elucidate the mechanisms underlying the differences in cytochrome P-450 function we have studied the 1'-hydroxylation of the prototype drug bufural...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90573-9
更新日期:1987-12-01 00:00:00
abstract::The O2 dependence of the metabolism of benzylamine to benzaldehyde, benzoate and hippurate was studied in isolated rat hepatocytes. The initial oxidation to benzaldehyde, catalyzed by monoamine oxidase, had an apparent Kmo2 value of 34 microM in cells and 40 microM in isolated rat liver mitochondria. The conversion of...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90234-x
更新日期:1984-02-01 00:00:00
abstract::The oxazaphosphorine agent cyclophosphamide (CP) is an alkylating agent with a relative low stem cell toxicity. The aim of this study was to further evaluate the stem cell toxicity of the active metabolites of CP and its structural analogue ifosfamide (IFO) in comparison to their antileukemic efficacy. Cells of differ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)00868-7
更新日期:2002-04-01 00:00:00
abstract::The effect of a choline-deficient diet on microsomal cytochrome P-450 and mixed-function oxidase (MFO) activity was investigated in relation to the development of nutritional cirrhosis. In rats that received the choline-deficient diet for 28 weeks cirrhosis was evident macroscopically and histologically; control rats ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90298-4
更新日期:1986-06-01 00:00:00
abstract::The need to protect human spermatozoa from oxidative stress during assisted reproductive technology, has prompted a detailed analysis of the impacts of phenolic compounds on the functional integrity of these cells. Investigation of 16 individual compounds revealed a surprising variety of negative effects including: (i...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.09.015
更新日期:2016-12-01 00:00:00
abstract::The N-type voltage-gated calcium channel (Ca(v)2.2) functions in neurons to regulate neurotransmitter release. It comprises a clinically relevant target for chronic pain. We have validated a calcium mobilization approach to assessing Ca(v)2.2 pharmacology in two stable Ca(v)2.2 cell lines: alpha1(B), alpha2delta, beta...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.06.003
更新日期:2006-09-14 00:00:00
abstract::We have previously shown that chronic administration of the 5-hydroxytryptamine (5-HT) receptor antagonist, ritanserin (10 mg/kg/day) or the monoamine oxidase type A inhibitor (MAOI), clorgyline (2 mg/kg/day), results in a reduction in 5-HT2 receptor number in rat cerebral cortex. This study investigates the effects o...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90242-d
更新日期:1990-11-01 00:00:00
abstract::Multidrug resistance-associated protein 2 (Mrp2) is an ATP-dependent export pump that mediates the formation of bile-salt-independent bile flow. Disruption of the canalicular localization of Mrp2, without changes in its expression, is observed in chronic liver failure and is accompanied by oxidative stress. We reporte...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.09.016
更新日期:2011-01-01 00:00:00
abstract::The interaction of the vasodilator, hydralazine, with the molybdenum hydroxylases, aldehyde oxidase and xanthine oxidase has been investigated. A potent progressive inhibition of rabbit liver aldehyde oxidase, in the presence of substrate, by low concentrations of hydralazine (0.1-1 microM) was observed in vitro but n...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90280-1
更新日期:1985-12-15 00:00:00
abstract::In the present study, the distribution and nature of esterases in the rat which hydrolysed fluazifop-butyl, carbaryl, paraoxon and phenylacetate were investigated. Vmax and Km values for the hydrolysis reactions were determined. Fluazifop-butyl was hydrolysed to fluazifop by rat liver (Vmax mumol/min/g microsomes 6.2 ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90373-5
更新日期:1993-01-07 00:00:00
abstract::The effects of nitroblue tetrazolium (NBT), a well-known scavenger of superoxide anions and an inhibitor of nicotinamide adenine dinucleotide (NADPH)-dependent oxidations, were assessed on the metabolism of glyceryl trinitrate (GTN) to nitric oxide (NO) by bovine aortic smooth muscle cells (SMC). The extent of this me...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90300-x
更新日期:1994-05-18 00:00:00
abstract::The present study investigated the presence of ryanodine receptors in the trematode Schistosoma mansoni. [3H]Ryanodine specific binding sites were found in the four subcellular fractions of S. mansoni; however, more binding sites were recovered in the heterogeneous fraction P1 and the microsomal fraction P4, as was th...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(98)00219-6
更新日期:1998-10-15 00:00:00
abstract::After partial hepatectomy (PHx), there are significant changes in the activity of a number of enzymes in the regenerating rat liver. Administration of low doses of recombinant human tumor necrosis factor-alpha (rHu-TNF) to normal rats induces similar changes in some of the enzymes but not in others. Because certain ob...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)00265-2
更新日期:1995-10-12 00:00:00
abstract::Bcr-abl kinase inhibitors have provided proof of principal that targeted therapy holds great promise for the treatment of cancer. However, despite the success of these agents in treating chronic myelogenous leukemia (CML), the majority of patients continue to present with minimal residual disease contained within the ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2010.04.003
更新日期:2010-09-01 00:00:00