Abstract：
:Previously, we reported that the multidrug resistance proteins MRP1, MRP2 and MRP3 confer resistance to therapeutic antifolates by mediating their cellular extrusion. We now determined whether MRPs also play a role in controlling cellular homeostasis of natural folates. In MRP1, MRP2 and MRP3-transfected 2008 human ovarian carcinoma cells total cellular folate content was 32-38% lower than in 2008 cells (105+/-14pmolfolate/mgprotein) when grown in medium containing 2.3 microM folic acid (FA). Under these conditions cellular growth rates were not compromised. However, when cells were challenged under folate-depleted conditions with a short exposure (4 hr) to FA or leucovorin, MRP1 and MRP3 overexpressing cells were impaired in their growth. In contrast to wild-type cells, MRP1 transfected cells retained only 60% of the maximum growth when exposed to 500 nM leucovorin or 500 microM FA. For 2008/MRP1 and 2008/MRP3 cells FA growth stimulation capacity was dramatically decreased when, during a 4 hr exposure, metabolism into rapidly polyglutamatable and retainable dihydrofolate was blocked by the dihydrofolate reductase inhibitor trimetrexate. To retain growth under such conditions MRP1 overexpressing cells required much higher concentrations of FA (EC(50) > 500 microM) compared to 2008 cells (EC(50): 12 microM). These results suggest that down- and up-regulation of MRP1 (and MRP3) expression can influence cellular folate homeostasis, in particular when cellular retention by polyglutamylation of folates is attenuated.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Hooijberg JH,Peters GJ,Assaraf YG,Kathmann I,Priest DG,Bunni MA,Veerman AJ,Scheffer GL,Kaspers GJ,Jansen Gdoi
10.1016/s0006-2952(02)01615-5subject
Has Abstractpub_date
2003-03-01 00:00:00pages
765-71issue
5eissn
0006-2952issn
1873-2968pii
S0006295202016155journal_volume
65pub_type
杂志文章abstract：:The mammalian thioredoxin reductase (TrxR) isoenzymes, TrxR1 in cytosol or nucleus, TrxR2 in mitochondria, and TrxR3 in testis, are essential seleno-flavoenzymes with a conserved penultimate selenocysteine (Sec) residue at the C-terminus, and have attracted increasing interests as potential targets for development of ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2015.12.004
更新日期：2016-02-15 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：:A major problem in the treatment of cancer is cellular resistance to cytotoxic drugs. In tumor cells in vitro, the development of multidrug resistance is usually accompanied by increased expression of drug transporters, either P-glycoprotein (P-gp) or multidrug resistance-associated protein (MRP(1)). Both proteins bel...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00453-6
更新日期：2000-11-15 00:00:00
abstract：:CYP2C19 (formerly known as CYP2C75), highly homologous to human CYP2C19, has been identified in cynomolgus and rhesus macaques, non-human primate species widely used in drug metabolism studies. CYP2C19 is predominantly expressed in liver and encodes a functional drug-metabolizing enzyme. Genetic variants in human CYP2...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.07.004
更新日期：2014-09-15 00:00:00
abstract：:Casein-elicited rat peritoneal polymorphonuclear leukocytes (PMNL) and rabbit platelets were prelabelled with [1-14C]arachidonic acid, and the effect of timegadine, a new anti-inflammatory agent, on the release and metabolism of arachidonic acid induced by A23187 (PMNL) and thrombin (platelets) was studied and compare...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90708-0
更新日期：1982-08-15 00:00:00
abstract：:Epidemiological and experimental animal data indicate that exposure to both metals and metalloid species exacerbates the risk of human diseases, particularly cancers. Vascular endothelial growth factor (VEGF), which performs a primary function in both tumor progression and angiogenesis, is up-regulated due to exposure...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.03.021
更新日期：2006-06-28 00:00:00
abstract：:The killing of isolated hepatocytes by N-acetyl-p-benzoquinone imine (NAPQI), the major metabolite of the oxidation of the hepatotoxin acetaminophen, has been studied previously as a model of liver cell injury by the parent compound. Such studies assume that the toxicity of acetaminophen is mediated by NAPQI and that ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90648-o
更新日期：1991-04-15 00:00:00
abstract：:Gemcitabine and ara-C have multiple mechanisms of action: DNA incorporation and for gemcitabine also ribonucleotide reductase (RNR) inhibition. Since dCTP competes with their incorporation into DNA, dCTP depletion can potentiate their cytotoxicity. We investigated whether additional RNR inhibition by Triapine (3-AP), ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.01.025
更新日期：2007-05-15 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：:Partial agonists for G protein-coupled receptors (GPCRs) provide opportunities for novel pharmacotherapies with enhanced on-target safety compared to full agonists. For the human adenosine A1 receptor (hA1AR) this has led to the discovery of capadenoson, which has been in phase IIa clinical trials for heart failure. A...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.114144
更新日期：2020-10-01 00:00:00
abstract：:The capacity of cultured bovine adrenal medullary cells to metabolize and export cyclic AMP has been studied. Basal cellular cyclic AMP levels were increased 50% by 100 microM 3-isobutyl-1-methylxanthine (IBMX) and rolipram, a class IV (cyclic AMP-specific) phosphodiesterase (PDE) inhibitor. They were not affected by ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90335-g
更新日期：1992-12-01 00:00:00
abstract：:In the present study we have investigated the effect of six antibiotics (penicillin G, ceftazidime, cephotaxime, cephoperazon, ampicillin and piperacillin) on the neutrophil cytolytic activity by using a system constituted of phorbol-12-myristate-13-acetate-triggered neutrophils and 51Cr-labelled lymphoblastoid Daudi ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90236-x
更新日期：1991-11-27 00:00:00
abstract：:In an effort to identify the human cytochromes P450 involved in the N-demethylation of dextromethorphan, the kinetics of 3-methoxymorphinan formation were studied in microsomal enzyme systems. Under initial rate conditions, 3-methoxymorphinan formation demonstrated single enzyme Michaelis-Menten kinetics using microso...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90237-2
更新日期：1994-07-05 00:00:00
abstract：:Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the fourth most frequent cause of cancer-related death worldwide. Sorafenib is the first line recommended therapy for patients with locally advanced/metastatic HCC. The low response rate is attributed to intrinsic resistance of HCC cell...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.113902
更新日期：2020-06-01 00:00:00
abstract：:The concentrations of dopamine (DA), m-tyramine (mTA), p-tyramine (pTA) and serotonin (5-HT) in the striata of rats 18 hr after the administration of three different doses (5, 50, or 100 mg/kg) of beta-phenylethylhydrazine (phenelzine, PEH) were measured. These concentrations were compared to those following the admin...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90475-6
更新日期：1983-05-01 00:00:00
abstract：:Glucose metabolism and hemoglobin reactivity in intact human erythrocytes were assessed in the presence of the tryptophan metabolites, 3-hydroxyanthranilate (3-HAT), quinolinate and picolinate. Of these compounds, only 3-HAT altered red cell oxidative status by inducing, in a dose-dependent manner, formation of methem...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90301-8
更新日期：1989-05-15 00:00:00
abstract：:The International Diabetes Federation predicts that by 2045 the number of individuals afflicted with diabetes will increase to 629 million. Furthermore, ∼352 million individuals with impaired glucose tolerance are at increased risk for developing diabetes. Several mechanisms have been proposed for the onset of metabol...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2018.04.026
更新日期：2018-08-01 00:00:00
abstract：:The peptide hormone gastrin binds two ferric ions with high affinity, and iron binding is essential for the biological activity of non-amidated gastrins in vitro and in vivo. Bi3+ ions also bind to glycine-extended gastrin17 (Ggly), but inhibit Ggly-induced cell proliferation and migration in gastrointestinal cell lin...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.11.030
更新日期：2012-02-15 00:00:00
abstract：:Eight naturally occurring prenylflavonoids were tested for their antiplatelet activities in rabbit platelet suspension. Cyclomorusin and artomunoxanthone showed strong inhibition of platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) induced platelet aggregation. Cyclomulberrin, dihydroiso...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-01-26 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：:Inflammatory bowel disease (IBD) is an incurable disease which affects millions of people in industrialized countries. Anecdotal and scientific evidence suggests that Cannabis use may have a positive impact in IBD patients. Here, we investigated the effect of cannabigerol (CBG), a non-psychotropic Cannabis-derived can...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2013.01.017
更新日期：2013-05-01 00:00:00
abstract：:To identify needed human equilibrative nucleoside transporter 4 (hENT4) inhibitors, we cloned and stably expressed the recombinant protein in PK15NTD (nucleoside transporter deficient) cells, and, investigated its interaction with a series of dipyridamole analogs synthesized in our laboratory. Compounds were tested in...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2013.08.063
更新日期：2013-12-01 00:00:00
abstract：:Carbon tetrachloride (CCl4)-induced inhibition of very low density lipoprotein (VLDL) secretion was studied in isolated hepatocytes. The hypothesis that inhibition of secretion is due to altered calcium homeostasis following CCl4-dependent inhibition of endoplasmic reticulum calcium sequestration was investigated. Inh...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90714-7
更新日期：1984-08-01 00:00:00
abstract：:Vanadate (VO3-) was found to activate adenylyl cyclase (AC) in ocular ciliary process membrane. This response was additive to that of isoproterenol (ISO) and vasoactive intestinal peptide (VIP), but it was potentiative with forskolin (FSK) and also with Ca2+/calmodulin activation of AC activity. The potentiated respon...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90284-4
更新日期：1993-03-24 00:00:00
abstract：:The population growth rate of HeLa cells treated with 60 microM 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) in reinforced Eagle's minimum essential medium was directly related to the concentration of fetal bovine serum in the range from 5 to 30%. Control cells proliferated at a maximal rate (doubling time: ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90306-x
更新日期：1984-02-15 00:00:00
abstract：:The effect of an inhibitor of protein kinase, HA1077 [1-(5-isoquinolinesulfonyl)-homopiperazine HCl], and its hydroxylated metabolite, HA1100, on the activation of NADPH oxidase in human neutrophils were studied. Cells were preincubated with each drug for 10 min and then activated by treatment with phorbol myristate a...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90116-e
更新日期：1993-10-19 00:00:00
abstract：:We studied the effect of DW2282-,[(S)-(+)-4-phenyl-1-[N-(4-aminobenzoyl)-indoline-5-sulfonyl-4,5-dihydro-2-imidazolone].hydrochloride], a newly developed anti-cancer agent, on cell proliferation, cell cycle progression, and induction of apoptosis in human promyelocytic leukemia (HL-60) cells. DW2282, a diarylsulfonylu...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00796-1
更新日期：2001-12-01 00:00:00
abstract：:H460 non-small cell lung, HCT116 colon and 4T1 breast tumor cell lines induced into senescence by exposure to either etoposide or doxorubicin were able to recover proliferative capacity both in mass culture and when enriched for the senescence-like phenotype by flow cytometry (based on β-galactosidase staining and cel...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.12.013
更新日期：2019-04-01 00:00:00
abstract：:Enzymatic N,O-acyltransfer of carcinogenic N-arylhydroxamic acids such as N-hydroxy-2-acetylaminofluorene (N-OH-AAF) results in the production of reactive electrophiles that can bond covalently with nucleophiles and also can cause inactivation of acyltransferase activity in a mechanism-based manner. Incubation of part...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90277-r
更新日期：1990-03-15 00:00:00
abstract：:We studied several steps of methionine metabolism in isolated rat hepatocytes both with and without the presence of a hepatotoxic agent (D-galactosamine). By use of selective labelling either on methyl or on carboxyl groups, we showed that intracellular methionine is used preferentially for the methylation of phosphol...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90699-4
更新日期：1986-12-01 00:00:00
