Abstract:
:During receptor-mediated endocytosis (RME), extracellular molecules are internalized after being recognized and bound to specific cell surface receptors. In previous studies of the asialoglycoprotein receptor (ASGPR) in rats, we showed that ethanol impairs RME at multiple ASGPR sites. Ethanol administration has been shown to increase apoptosis, and we demonstrated increased sensitization to apoptotic induction in hepatocytes from ethanol-fed rats. Although a physiological role for the ASGPR has not been identified, investigators have shown its involvement in the uptake/clearance of apoptotic cells in vitro. This suggests a potential role for the ASGPR in the removal of apoptotic cells, and the recent availability of an ASGPR-deficient mouse strain provides an excellent opportunity to examine the role of the ASGPR during ethanol impairment. In this study, we examined ethanol-impaired RME in mice and began the characterization of ASGPR-deficient mice for use in ethanol studies. Similar to our findings with rats, ligand binding, internalization, and degradation were decreased 45-50% in hepatocytes from ethanol-fed wild-type mice. In ASGPR-deficient mice, these parameters did not vary among the chow-fed, pair-fed control, or ethanol groups and were negligible compared with those of wild-type mice. TUNEL analysis of liver sections showed an ethanol-induced increase in apoptotic bodies in all mouse strains with a significant difference in the receptor-deficient mice. Further, the livers of ASGPR-deficient mice had three times more apoptotic bodies, in all feeding groups, compared with wild-type mice. These results support the use of the ASGPR-deficient mouse model for studying ethanol-induced liver injury, specifically ethanol-induced apoptosis.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Dalton SR,Wiegert RL,Baldwin CR,Kassel KM,Casey CAdoi
10.1016/s0006-2952(02)01555-1subject
Has Abstractpub_date
2003-02-15 00:00:00pages
535-43issue
4eissn
0006-2952issn
1873-2968pii
S0006295202015551journal_volume
65pub_type
杂志文章abstract::A method is described for the measurement of the polyglutamates of the quinazoline thymidylate synthase inhibitor, N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin- 6-ylmethyl)-N-methylamino]-2-theonyl)-L-glutamic acid (ICI D1694). This involved incubation of cells with [5-3H]ICI D1694, extraction of the polyglutamates a...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90170-2
更新日期:1993-02-24 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 effects of 2,5-hexanedione (2,5 HD) on skeletal proteins of red blood cells (RBCs) were investigated both in vitro (human RBCs) and in vivo in male Sprague-Dawley rats which had been treated with the drug for several days. We found that 2,5 HD induced the following major changes in the electrophoretic pattern of t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90557-1
更新日期:1989-08-15 00:00:00
abstract::The alcohol-avoiding ANA (Alko, Non-Alcohol) and alcohol-preferring AA (Alko, Alcohol) rat lines are known to differ in their acetaldehyde metabolism and were originally found to differ in hepatic alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities in the 1970s. At the beginning of the 1980s, thes...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90199-6
更新日期:1994-10-18 00:00:00
abstract::This study demonstrates that the exposure of phenobarbitone-treated rats to halothane at an oxygen concentration of either 10% or 14% results in marked decreases in cytochrome P-450 content and aminopyrine demethylase activity in animals sacrificed from 1 to 48 hr post-exposure. The alterations observed in the hepatic...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90182-1
更新日期:1987-03-15 00:00:00
abstract::Flavonoids are constituents of fruits, vegetables, and plant-derived beverages, as well as components in herbal containing dietary supplements. They exhibit a remarkable spectrum of biochemical and pharmacological activities. In this study, we examined morin (3,5,7,2',4'-pentahydroxyflavone) for its effect on 12-O-tet...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2005.03.008
更新日期:2005-06-01 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::Recent experiments from our laboratory have indicated that the inhibitory effect of 3'-azido-3'-deoxythymidine (AZT) on oxidative phosphorylation may occur directly, in addition to being brought about by its inhibition of mtDNA replication. We report here studies on the effect of AZT on adenylate kinase, an enzyme cru...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90564-9
更新日期:1994-10-07 00:00:00
abstract::When human saliva obtained after cigarette smoking was incubated in the presence of tryptamine, the formation of 1,2,3,4-tetrahydro-beta-carboline (TBC) and 1-methyl-1,2,3,4-tetrahydro-beta-carboline (MTBC) was observed in a short time. After incubation with tryptamine (2.5 micrograms/microliter) for 10 min, the conce...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02068-3
更新日期:1995-12-22 00:00:00
abstract::An intestinal active transport system specific to small peptides and peptide-like drugs such as beta-lactam antibiotics was functionally expressed in Xenopus laevis oocytes after microinjection of messenger RNA (mRNA) derived from rat intestinal mucosal cells. The transport activity was evaluated by measuring the upta...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90358-1
更新日期:1994-08-30 00:00:00
abstract::Miconazole and clotrimazole, members of a class of imidazole agents which have broad spectrum antimycotic activity, were shown to be potent inhibitors of steroid aromatase activity of human placental microsomes. The I50 values for the inhibition of aromatase activity by miconazole, clotrimazole, ketoconazole, and amin...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90613-6
更新日期:1985-04-01 00:00:00
abstract::Selective antagonists for the adenosine A(3) receptor (A3AR), a member of the G protein-coupled receptors, have been indicated as potential drugs for anti-asthma or anti-inflammation. However, potent antagonists for the rodent A3AR have not been identified. To evaluate the pharmacological effects of human A3AR antagon...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2005.08.003
更新日期:2005-11-15 00:00:00
abstract::Ephedrine and its alkaloids are used for the treatment of asthma, nasal congestion, and obesity. Ephedrine, with two chiral centers, exists as four isomers that exhibit direct and indirect effects on both alpha- and beta-adrenergic receptors (AR). Our main goal was to study the direct effects of the ephedrine isomers ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00152-5
更新日期:1999-09-01 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::25-Hydroxycholesterol stimulated acyl-CoA:cholesterol acyltransferase (ACAT) activity in rat liver microsomes in vitro with half-maximal stimulation at 16.8 microM oxysterol and a maximal activity that was three times that in its absence. The current study was conducted to determine the effect of 25-hydroxycholesterol...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(96)00649-1
更新日期:1997-01-10 00:00:00
abstract::Microsomal and cytosolic epoxide hydrolase (mEH and cEH respectively) and glutathione S-transferase (GST) activities were measured in the liver, kidney, and gills of rainbow trout. Assays were optimized for time, pH, and temperature, using trans-stilbene oxide (TSO) and cis-stilbene oxide (CSO) as substrates for cEH a...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90275-x
更新日期:1989-03-15 00:00:00
abstract::Tirapazamine (SR 4233) is a bioreductive antitumour drug in Phase III clinical trial which is activated in hypoxic tumour regions to generate a cytotoxic species. Electron paramagnetic resonance (EPR) spectrometry was used to investigate directly the formation of free radicals as the result of tirapazamine reduction b...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00487-1
更新日期:2000-12-15 00:00:00
abstract::Glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGTs), is a crucial substance metabolism and elimination process that mostly occurs in the liver to protect the body from toxic substances and maintain homeostasis. The reaction functions well in a uridine diphosphate glucuronic acid (UDPGA) -dependent manner...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2019.113753
更新日期:2020-02-01 00:00:00
abstract::A strain of hyperlipidaemic Sprague-Dawley (HSD) rat was compared with normal Sprague-Dawley (SD) rats for expression of cholesterol 7alpha-hydroxylase activity (CYP7A1) and other cytochrome P450 (P450) enzymes in liver. Hepatic microsomal CYP7A1 activity in male HSD rats was 2-3-fold lower than in male SD rats with C...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(98)00015-x
更新日期:1998-07-15 00:00:00
abstract::LLC-PK1 cells have been used as an in vitro model to study the nephrotoxicity of the antitumor drug cisplatin. A concentration-dependent cytotoxicity of cisplatin, measured as lactate dehydrogenase leakage and amount of protein remaining attached to the culture plate, was observed. At a cisplatin concentration of 0.4 ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90024-d
更新日期:1992-07-22 00:00:00
abstract::The role of nitric oxide (NO)/guanosine 3',5'-cyclic monophosphate (cGMP) signaling pathway in the regulation of fatty acid metabolism was investigated in rat hepatocytes. Treatment with NO donors, which are known to activate soluble guanylyl cyclase, inhibited in parallel fatty acid synthesis de novo and acetyl-CoA c...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)01623-4
更新日期:2003-03-01 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 aim of this study was to find the peptide ligands to inhibit Candida albicans secreted aspartyl proteinase 2 (Sap2). First, a ligand library, containing 300 different peptides, was constructed, and their interaction with Sap2 was separately calculated by molecular dynamic software. Second, 10 peptide ligands with ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2014.05.020
更新日期:2014-08-15 00:00:00
abstract::A newly-synthesized derivative of prazosin, prazosinamine hydrochloride, was examined for its ability to antagonize the interaction of the alpha 1-adrenergic agonist phenylephrine with liver cells. Using a Ca2--selective electrode to measure changes in perfusate Ca2+ concentration, prazosinamine was found to be as eff...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90040-2
更新日期:1987-05-15 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::Specific binding of 35S-t-butylbicyclophosphorothionate (TBPS) was studied in synaptosomal membranes of rat cerebral cortex under nonequilibrium conditions. TBPS binding proved to be suitable for the characterization of not only the efficacy but also the potency of benzodiazepine (BZ) receptor ligands in vitro. Five B...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90581-3
更新日期:1988-06-01 00:00:00
abstract::The in vitro and in vivo effects of fluoxetine (and its active metabolite norfluoxetine) on mitochondrial respiration and F0F1-ATPase were studied, respectively, in mitochondria and submitochondrial particles isolated from rat liver. Fluoxetine in vitro inhibited state 3 mitochondrial respiration for alpha-ketoglutara...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90283-6
更新日期:1994-08-03 00:00:00
abstract::Oridonin is a diterpene compound that regulates the activity of PPAR-γ (peroxisome proliferator-activated receptor gamma) transcription factor. Cumulative evidence indicates that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors (AMPARs) play an important role in the treatment of de...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.114136
更新日期:2020-10-01 00:00:00
abstract::Recently, accumulated statistical data indicate the protective effect of caffeine consumption against several types of cancer diseases. There are also reports about protective effect of caffeine and other xanthines against tumors induced by polycyclic aromatic hydrocarbons. One of the explanations is based on biologic...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00904-2
更新日期:2002-02-15 00:00:00
abstract::Corticosteroid esters have been encapsulated into intact erythrocytes and used as an intravenous treatment for adjuvant induced arthritis in the rat. The treatment consisted of injections of the encapsulated steroids with the effects monitored for up to 14 days. On an equivalent weight basis both encapsulated cortisol...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90362-3
更新日期:1983-11-15 00:00:00