Abstract：
:The biological effects of 1-methyl-2-nitrosoimidazole (INO), the 2 electron reduction product of biologically active 1-methyl-2-nitroimidazole, were examined in HT-29 human colon cancer cells by clonogenic assay and glutathione (GSH) determination. INO was very toxic towards HT-29 cells and was equally toxic under aerobic and hypoxic conditions. Cytotoxicity was highly dependent on cell concentration, decreasing as cell concentration increased. INO also resulted in an initial dose-dependent depletion of intracellular GSH which plateaued when the GSH content of INO-treated cells reached approximately 8% of control levels. As was the case for cytotoxicity, the magnitude of GSH depletion by any given INO dose was highly dependent on cell concentration, being greatest at low cell densities. Both toxicity and GSH depletion were more pronounced when cells were exposed in culture medium without the reducing agent, ascorbate. HT-29 cells preincubated with the GSH synthesis inhibitor, buthionine sulfoximine (BSO), to reduce GSH levels to approximately 10% of control levels were more sensitive to subsequent INO exposure. These data suggest that the nitroso- reduction product of 2-nitroimidazoles may be responsible for cytotoxicity and glutathione depletion associated with hypoxic exposure to 2-nitroimidazoles.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Mulcahy RT,Gipp JJ,Ublacker GA,Panicucci R,McClelland RAdoi
10.1016/0006-2952(89)90315-8subject
Has Abstractpub_date
1989-05-15 00:00:00pages
1667-71issue
10eissn
0006-2952issn
1873-2968pii
0006-2952(89)90315-8journal_volume
38pub_type
杂志文章abstract：:Activation of the transcription factor NF-kappaB is known to be important in the regulated expression of a large number of pro-inflammatory genes including interleukin-8 (IL-8). Previously, we showed that the protein kinase inhibitor staurosporine potentiates IL-1-stimulated IL-8 production in human keratinocytes. Mor...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00117-8
更新日期：1998-07-01 00:00:00
abstract：:The transcription factor NF-kappaB plays a key role in a wide variety of cellular processes such as innate and adaptive immunity, cellular proliferation, apoptosis and development. In unstimulated cells, NF-kappaB is sequestered in the cytoplasm through its tight association with inhibitory proteins called IkappaBs, c...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2006.06.017
更新日期：2006-10-30 00:00:00
abstract：:Phomopsins comprise a family of peptide mycotoxins containing a 13-membered ring formed by an ether bridge, produced by the fungus Phomopsis leptostromiformis, the causal agent in lupin poisoning (lupinosis). The biochemical actions of two naturally occurring phomopsins, phomopsin A and B, and the chemical derivatives...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90141-9
更新日期：1987-07-01 00:00:00
abstract：:The incidence, severity and progression of autoimmune diseases (e.g. scleroderma, multiple sclerosis, rheumatoid arthritis) and certain inflammatory diseases (e.g. asthma) are sex-biased where these pathologies dominate in women. However, other immune disorders such as sepsis, post-surgery infections and gout display ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2017.06.128
更新日期：2017-12-01 00:00:00
abstract：:The influence of anionic groups on interaction of nucleophilic sulfur compounds with the purified hog liver flavin-containing monooxygenase was evaluated from kinetic constants obtained with various dithiobenzoates, thiolbenzoates, and thiolalkylcarboxylic acids. All compounds tested bearing a single negative charge l...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90391-1
更新日期：1987-01-01 00:00:00
abstract：:Snake venom three-finger α-neurotoxins (α-3FNTx) act on postsynaptic nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction (NMJ) to produce skeletal muscle paralysis. The discovery of the archetypal α-bungarotoxin (α-BgTx), almost six decades ago, exponentially expanded our knowledge of membrane rec...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2020.114168
更新日期：2020-11-01 00:00:00
abstract：:Microsomal epoxide hydrolase (mEH) catalyzes the hydrolysis of epoxide intermediates derived from drugs and environmental chemicals. The response of in vivo (embryo) and in vitro (embryo fibroblast) tests were analyzed using mEH-null and wild-type mice to determine the relative role of maternal and embryonic mEH in th...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)00847-x
更新日期：2002-03-15 00:00:00
abstract：:Resveratrol, a natural phytoalexin that shows health-promoting benefits, is an inhibitor of store-operated calcium entry (SOCE). Knowledge of the molecular mechanism underlying this inhibition is required for the proper design of therapies that include resveratrol or related stilbenoids, but remains largely unknown. T...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2013.09.018
更新日期：2013-12-01 00:00:00
abstract：:The enhanced nitric oxide (NO) and prostaglandin (PG) generation of activated macrophages is controlled by glucocorticoid-sensitive inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. Negative feedback regulation of iNOS expression by the products of both pathways has been suggested, but...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(96)00737-x
更新日期：1997-02-21 00:00:00
abstract：:The uptake of iron by the liver and cerebellum was measured in rats using [59Fe]transferrin. An acute ethanol load (50 mmol/kg body wt., i.p.) elicited a significant increase in the hepatic and cerebellar non-heme iron concentration. The uptake of 59Fe by the liver and the cerebellum was significantly greater in the e...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90313-1
更新日期：1994-05-18 00:00:00
abstract：:We tested the ability of a wide variety of organic compounds, including benzene and phenol derivatives, aromatic amines, pyrazoline derivatives and other non-steroidal anti-inflammatory drugs, to act as cosubstrates during the horseradish peroxidase/hydrogen peroxide-mediated oxygenation of arachidonic acid. Structura...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90326-2
更新日期：1989-04-15 00:00:00
abstract：:The so-called human xenosensors, constitutive androstane receptor (hCAR), pregnane X receptor (hPXR) and aryl hydrocarbon receptor (hAhR), participate in drug metabolism and transport as well as in several endogenous processes by regulating the expression of their target genes. While the ligand specificities for hPXR ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.08.027
更新日期：2011-12-15 00:00:00
abstract：:The formation of morphine glucuronides is enantio- and regioselective in rats and humans. In rat liver microsomes, natural (-)-morphine formed only the 3-O-glucuronide, whereas the unnatural (+)-morphine formed glucuronides at both the 3-OH and 6-OH positions, with the 6-O-glucuronide being the principal product. In h...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90625-4
更新日期：1989-10-01 00:00:00
abstract：:Anandamide and 2-arachidonoylglycerol (2-AG) are two endogenous ligands for the cannabinoid receptors, and their cannabimimetic activities are lost when they are hydrolyzed enzymatically. Cytosol and particulate fractions of porcine brain exhibited a high 2-AG hydrolyzing activity of 100 nmol/min/mg protein. Most of t...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00314-1
更新日期：1999-02-15 00:00:00
abstract：:The beta-adrenoceptor blocking properties of vaninolol ((+/-)4-[4'-(2-hydroxy-3-tert-butyl-aminopropoxy)-3'-methoxyphenyl]- 3-buten-2-one), derived from vanillin, were first investigated under in vivo and in vitro conditions. Vaninolol (0.1, 0.5, 1.0 mg/kg, i.v.), as well as propranolol, produced a dose-dependent brad...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-07-05 00:00:00
abstract：:Tumor necrosis factor (TNF) is a pleiotropic cytokine that mediates different cellular responses including cytotoxicity, cytostasis, proliferation, differentiation and expression of specific genes. Recent studies have demonstrated that chemotherapeutic drugs that inhibit the nuclear enzyme DNA topoisomerase II synergi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90468-c
更新日期：1993-10-05 00:00:00
abstract：:The GABA(B) receptor was the first heteromeric G-protein coupled receptor (GPCR) identified. Indeed, both GABA(B1) and GABA(B2) subunits appear necessary to get a functional GABA(B) receptor. Soon after the cloning of both subunits, it was demonstrated that GABA(B2) was required for GABA(B1) to reach the cell surface....
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.06.035
更新日期：2004-10-15 00:00:00
abstract：:In this study, we showed that oligogalacturonic acid (OGA) purified from flax pectin inhibit in vitro osteoclastic bone resorption in a dose-dependent manner. The OGA inhibitory effect was neither linked to an effect on osteoclast apoptosis, nor to an inhibition of cathepsin K activity. By means of an in vitro collage...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.07.014
更新日期：2009-12-15 00:00:00
abstract：:The aim of this study was to test if human platelet leukotriene C4-synthase (LTC4-S) is pharmacologically different from cloned and expressed LTC4-S and, in light of the significant homologies between 5-lipoxygenase activating protein (FLAP) and LTC4-S, if different potencies of leukotriene synthesis inhibitors acting...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(96)00819-2
更新日期：1997-03-21 00:00:00
abstract：:To investigate the potential interactions between the angiotensin II (Ang II) and insulin signaling systems, regulation of IRS-1 phosphorylation and insulin-induced Akt activation by Ang II were examined in clone 9 (C9) hepatocytes. In these cells, Ang II specifically inhibited activation of insulin-induced Akt Thr(30...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.10.014
更新日期：2010-03-01 00:00:00
abstract：:This investigation suggests that the oxazolidine derivative of propranolol is a prodrug which is hydrolysed stereoselectively to propranolol by hepatic post-mitochondrial supernatant. The (S)-form of the prodrug is more stable in the biological system than its (R)-form. ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90113-j
更新日期：1991-05-01 00:00:00
abstract：:The mechanism by which the substituted benzimidazole sulphoxide BY 1023/SK&F 96022 inhibited the (H+ + K+)-ATPase, the enzyme responsible for hydrogen ion secretion in the stomach, was studied in a variety of in vitro preparations. In gastric preparations that were capable of active hydrogen ion transport with consequ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90128-8
更新日期：1990-06-01 00:00:00
abstract：:Cells commonly resist growth inhibition by purine and pyrimidine bases and nucleosides by restricting intracellular formation of the corresponding 5'-mononucleotides. Nucleotide derivatives that can act as effective membrane-transport precursors of the poorly membrane-permeable nucleotides have not been identified so ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90613-8
更新日期：1989-10-01 00:00:00
abstract：:In a previous report we described the export of hyaluronan from Streptococcus pyogenes by an ABC transporter. Extending these findings a sequence homology search against human proteins revealed a strong homology to the multidrug resistance transporter ABC-B (MDR-1) and ABC-C (MRP 5). Using several inhibitors directed ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.06.017
更新日期：2004-10-01 00:00:00
abstract：:These in vitro studies indicate that N-oxidation of N-hydroxyamphetamine (NOHA) by rat liver homogenates yields phenylacetone oxime (PAOx) as the major metabolite. This oxidation was NADPH and oxygen dependent but was not appreciably increased in microsomes from phenobarbital-pretreated animals. The addition to micros...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90244-1
更新日期：1982-01-01 00:00:00
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 influence of various concentrations of ferrous iron and ascorbate on in vitro peroxidation and drug binding of diverse membrane preparations (cerebral cortex and liver) was studied. Peroxidation was not simply dose-related to ascorbate and ferrous iron, but a complex relationship between iron and ascorbate when ad...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)02058-6
更新日期：1995-11-27 00:00:00
abstract：:Adenosine (Ado, 10 microM) did not inhibit ADP-induced human platelet aggregation in whole blood. However, if the blood was preincubated with dipyridamole (10 microM), a potent inhibitor of the erythrocytic nucleoside transport system (NTS), Ado acted as a strong inhibitor of platelet aggregation. Similarly, Ado inhib...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90373-9
更新日期：1985-11-15 00:00:00
abstract：:The pharmacokinetics and biochemical effects of the uridine phosphorylase (UrdPase) inhibitor 5-benzylacyclouridine (BAU) were investigated in the mouse, rat and monkey. Following i.p. administration of BAU (30 mg/kg) in the mouse and i.v. administration in the rat and monkey, initial BAU plasma half-life values were ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90390-i
更新日期：1993-01-07 00:00:00
abstract：:This study was designed to examine the relationship between the extent of Sandimmun (cyclosporin A, SIM) metabolism and SIM-induced hepatotoxicity both in vivo and in primary cultures of rat hepatocytes. Firstly, SIM (50 mg/kg p.o.) was administered daily to male Wistar rats for 10 days with or without co-administrati...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90024-f
更新日期：1990-01-15 00:00:00
