Abstract:
:The mechanism of activation of microsomal glutathione transferase in isolated liver cells by diisapropylidene acetone (phorone) was investigated. Phorone (1 mM) causes a time-dependent increase (up to 2.6-fold) in the glutathione transferase activity of microsomes isolated from treated hepatocytes. Since phorone reacts with sulfhydryl groups, the possibility that this compound activated microsomal glutathione transferase directly was studied. It was found that neither the activity of the purified enzyme nor that in isolated microsomes is affected by phorone. It has been suggested [Masukawa T and Iwata H, Biochem Pharmacol 35: 435-438, 1986] that activation of microsomal glutathione transferase by phorone in vivo is mediated through thiol-disulfide interchange involving oxidized glutathione (GSSG). It is shown here that the glutathione transferase activity of isolated microsomes, which was increased by the addition of 10 mM GSSG, can be decreased to the basal level with 0.1 M dithioerythritol. Dithioerythritol, on the other hand, only marginally decreases the glutathione transferase activity in microsomes isolated from phorone-treated hepatocytes. This finding argues against a role for thiol-disulfide interchange in the activation of the enzyme by phorone. Furthermore, the glutathione depletion caused by phorone does not seem to be responsible for activation per se, since other thiol depletors [e.g. diethylmaleate (DEM)] do not affect the activity of the enzyme. Immunoblot analysis of microsomes isolated from phorone-treated hepatocytes did not reveal any partial proteolysis which might have accounted for the activation. It is suggested that activation of microsomal glutathione transferase by phorone proceeds through a mechanism which might reflect an in vivo regulation of this enzyme. Additional compounds which have been shown to activate the microsomal glutathione transferase in vivo were also tested and significant activation was obtained with 1,2-dibromoethane (1.4-fold) but not with DEM or carbon tetrachloride. Activation was also obtained with 1-chloro-2,4-dinitrobenzene (CDNB) (1.6-fold) and to a small extent with t-butyl hydroperoxide (1.2-fold). The activation by 1,2-dibromoethane and CDNB is probably mediated through covalent binding, considering the known alkylating properties of these compounds. CDNB is the first substrate shown to activate the microsomal glutathione transferase implying that electrophilic compounds which are substrates can increase the rate of their own elimination by reacting with this enzyme. In addition, activation by t-butyl hydroperoxide indicates that oxidative stress can activate microsomal glutathione transferase.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Lundqvist G,Morgenstern Rdoi
10.1016/0006-2952(92)90269-osubject
Has Abstractpub_date
1992-01-22 00:00:00pages
131-5issue
2eissn
0006-2952issn
1873-2968pii
0006-2952(92)90269-Ojournal_volume
43pub_type
杂志文章abstract::This study reports an investigation on the effect of the seleno-organic compound ebselen on rat liver mitochondria. We show that low concentrations of ebselen induced an increase in rat liver mitochondrial membrane permeability, resulting in swelling and loss of membrane potential. These effects were mediated by the o...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00114-x
更新日期:2003-05-15 00:00:00
abstract::The effects of propranolol or phentolamine on the metabolism of phospholipids, diacylglycerol, and triacylglycerol were studied in the bovine retina in vitro. Lipid labeling was followed during short-term incubation of intact bovine retinas with [U-14C]glycerol and [1-14C]palmitic acid. Each of these precursors was re...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90341-0
更新日期:1982-03-15 00:00:00
abstract::B-Raf kinase is the key point in a main branch of mitogen-activated protein kinase pathways and some of its mutations, such as the V600E mutation, lead to the persistent activation of ERK signaling and the trigger of severe diseases, including melanoma and other somatic cancers. Several potent drugs have been approved...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2017.02.022
更新日期:2017-05-15 00:00:00
abstract::The present study was designed to investigate the effect of hepatic glutathione depletion induced by intraperitoneal administration of diethyl maleate (DEM) on the maximum biliary transport (Tm) and on the biliary excretion of bromosulfophthalein (BSP) in anaesthetized rabbits when the dye was perfused endovenously at...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90784-8
更新日期:1988-04-01 00:00:00
abstract::Griseofulvin is an anti-fungal drug whose mechanism of action is directed against microtubules. Although it inhibits the assembly of mammalian brain tubulin, its binding to tubulin has not been directly measured successfully. We have examined the interaction of griseofulvin with tubulin fluorometrically by measuring t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02406-9
更新日期:1996-04-12 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::The chemotherapeutic drug cisplatin is an important treatment for many types of solid tumours, in particular non-small cell lung cancer (NSCLC). Platinum(IV) complexes offer several advantages to cisplatin due to their requirement for reduction to the active platinum(II) form to elicit cytotoxicity. This should minimi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2005.07.016
更新日期:2005-10-15 00:00:00
abstract::Human leukemia K562 and HeLa cells were treated with daunomycin (DA) for 1-4 hr. With the indirect immunofluorescence technique, we observed that the nucleolar protein nucleophosmin/B23 (NPM) shifted its location from the nucleolus to the nucleoplasm (NPM-translocation). The degree of NPM-translocation was determined ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00043-x
更新日期:1999-06-01 00:00:00
abstract::The effect of the cationic dye, ruthenium red (RR), on ionic fluxes, Ca2+ signal generation, and stimulation of aldosterone production was studied in isolated rat adrenal glomerulosa cells. In these cells, increased extracellular [K+] as well as angiotensin II (Ang II) elevate cytoplasmic Ca2+ concentration and thereu...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(98)00285-8
更新日期:1999-01-15 00:00:00
abstract::Various agents stimulate the secretion of lung surfactant from alveolar type II cells by increasing intracellular Ca2+, cyclic adenosine-3':5'-monophosphate (cAMP), or diacylglycerol. A few agents, including the purified surfactant protein A, are known to inhibit the secretion by an unknown mechanism. In the present s...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90450-b
更新日期:1993-05-05 00:00:00
abstract::Phenylethanolamine-N-methyltransferase (PNMT) catalyzes the conversion of norepinephrine to epinephrine. The enzyme, obtained from bovine adrenal gland, was incubated with PbCl2 at 23 degrees for various times prior to assay at 37 degrees. Inhibition developed slowly and reached a maximum after 45 min. In the presence...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90409-9
更新日期:1982-06-01 00:00:00
abstract::The role of CYP2E1 in ketone-stimulated insulin release was investigated using isolated pancreatic islets of Langerhans and two mammalian insulin secreting pancreatic beta-cell lines engineered to stably express human CYP2E1 (designated BRIN BD11h2E1 and INS-1h2E1). Isolated rat pancreatic islets were shown to express...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2003.10.011
更新日期:2004-03-01 00:00:00
abstract::The metabolism of 2-acetylaminofluorene (AAF) to its six oxidative metabolites has been used to investigate the effect of dexamethasone on cytochrome P-450 activity in cultured rat hepatocytes. In control hepatocytes the metabolism of AAF to its 1-, 5-, 7-, 9- and N-hydroxylated metabolites rapidly declined in culture...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90695-2
更新日期:1987-01-15 00:00:00
abstract::Acetoacetyl-CoA synthetase (AACS, acetoacetate-CoA ligase, EC 6.2.1.16) is a ketone body-utilizing enzyme, the physiological role of which remains unclear yet in mammals, particularly has never been studied in human. In order to investigate the tissue distribution of AACS in human, cDNA encoding AACS was isolated from...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)01656-8
更新日期:2003-03-15 00:00:00
abstract::The spontaneous autoxidation of the neurotoxin 6-hydroxydopamine proceeds by a free radical chain reaction involving the superoxide anion radical and produces the corresponding chromogen 6-hydroxydopamine quinone and hydrogen peroxide. The rate of this reaction is increased in the presence of ceruloplasmin and peroxid...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0006-2952(96)00716-2
更新日期:1997-04-25 00:00:00
abstract::Exposure of lung tissue to Co(II) ions both in vivo and in vitro results in toxicity, a relatively early event of which is the oxidation of cellular glutathione. In this study we have attempted to delineate the relationship between this oxidation of glutathione and the subsequent development of cellular dysfunction. S...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90573-2
更新日期:1992-02-04 00:00:00
abstract::Mevinolin is a potent competitive inhibitor of HMG-CoA reductase, the enzyme catalyzing the major rate-limiting step in cholesterol synthesis. In this study the drug was administered as an intragastric dose at 2.5 mg/kg/day to 10 to 12-week-old lean and obese Zucker female rats over a 5-day period. Mevinolin showed no...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90179-1
更新日期:1987-03-15 00:00:00
abstract::Disturbed redox homeostasis with both elevated reactive oxygen species (ROS) levels and antioxidant defense mechanisms has been reported in acute lymphoblastic leukemia (ALL). We therefore hypothesized that inhibition of pathways responsible for ROS detoxification renders ALL cells more susceptible for cell death. Her...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.01.004
更新日期:2016-04-01 00:00:00
abstract::The effects of the P2-purinoceptor antagonist, suramin, on ADP-induced increases in human platelet cytosolic calcium concentration ([Ca2+]i) and inhibition of prostaglandin E1 (PGE1)-stimulated adenylate cyclase activity were investigated. Suramin (50-200 microM) acted as an antagonist of ADP-induced increases in [Ca2...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90412-x
更新日期:1994-03-15 00:00:00
abstract::The anticancer drug cis-diamminedichloroplatinum(II) (cisplatin) has been shown previously to form adducts preferentially within internucleosomal or linker DNA rather than to DNA within the nucleosome. To determine whether other "open" regions of chromatin have an increased affinity for cisplatin, adduct formation wit...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(95)02256-2
更新日期:1996-03-08 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::African trypanosomes, like Trypanosoma brucei, depend on antigenic variation to evade the immune response of the vertebrate host. An antigenic switch corresponds to the activation of a variable surface glycoprotein (VSG) gene from a large silent repertoire. Most switches require the duplicative transposition of a VSG ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90208-4
更新日期:1985-12-01 00:00:00
abstract::A 1.57kb BamH1 fragment containing a full-length human debrisoquine 4-hydroxylase cytochrome P450 (CYP2D6) cDNA was inserted into the BglII site of the yeast expression plasmid pMA91 and the resulting recombinant plasmid, PELT1, introduced into Saccharomyces cerevisiae strain AH22. Microsomes prepared from AH22/pELT1 ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90394-x
更新日期:1992-08-18 00:00:00
abstract::The present investigation addressed the role of verapamil for oral pharmacokinetics of morphine-6-beta-glucuronide (M6G). Male Sprague-Dawley rats received 62.5 mg kg(-1) M6G-dihydrate orally w/wo pre-treatment with 70 mg kg(-1) verapamil. Intravenous M6G (3.9 mg kg(-1) ) and oral morphine (52.7 mg kg(-1) morphine-hyd...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)00881-x
更新日期:2002-04-15 00:00:00
abstract::The increase in life expectancy has resulted in a high occurrence of dementia and Alzheimer's disease (AD). Research on AD has undergone a paradigm shift from viewing it as a disease of old age to taking a life course perspective. Several vascular, lifestyle, psychological and genetic risk factors influencing this lat...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2014.01.003
更新日期:2014-04-15 00:00:00
abstract::Class B peptide hormone GPCRs are targets for the treatment of major chronic disease. Peptide ligands of these receptors display biased agonism and this may provide future therapeutic advantage. Recent active structures of the calcitonin (CT) and glucagon-like peptide-1 (GLP-1) receptors reveal distinct engagement of ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.02.005
更新日期:2018-04-01 00:00:00
abstract::Hypertension is considered as one of the cancer progressive factors, and often found comorbidity in cancer patients. Renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure, and angiotensin II (Ang II) is well known pressor peptide associated with RAS. Ang II has been reported to acc...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.04.012
更新日期:2018-08-01 00:00:00
abstract::Naproxen, a non-steroidal anti-inflammatory drug, is known to be highly effective and relatively safe, but some side-effects in the liver have been reported. In the present study, the effect of naproxen metabolism on rat liver microsomes was studied by determining lipid peroxidation in terms of thiobarbituric acid rea...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90315-n
更新日期:1993-04-22 00:00:00
abstract::A significant concentration-dependent difference was found between beta-adrenoceptor blocking drugs in their ability to inhibit A23187-induced isolated platelet aggregation. In the absence of extracellular calcium ions the following rank order of potency to inhibit calcium ionophore stimulated platelet aggregation was...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90257-7
更新日期:1994-06-15 00:00:00
abstract::The addition of agents, such as tumor necrosis factor-alpha, to human peripheral neutrophils (HPPMN) induces priming, which enhances the receptor-mediated superoxide (O2-) generation and tyrosine phosphorylation of several HPPMN proteins. Lidocaine, a local anesthetic, inhibited both enhanced O2- generation and tyrosi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90299-c
更新日期:1993-04-22 00:00:00