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. Simultaneous incubation with H2O2 potentiated Co(II)-induced increases in both levels of oxidized glutathione (GSSG) and the activity of the pentose phosphate pathway in hamster lung slices. This effect was initially synergistic and, thereafter, both parameters were maintained at significantly greater levels than with either treatment alone throughout the incubation period until the onset of detectable cellular dysfunction. When dysfunction occurred, however, it was not quantitatively increased by the co-treatment over that occurring with CoCl2 alone. Similarly, pretreatment of slices with the glutathione reductase inhibitor 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) potentiated the Co(II)-induced increase in levels of GSSG. However, this effect was again not associated with an enhancement of cell dysfunction. Since the Co(II)-induced cell damage appeared not to be related directly to the oxidation of glutathione, the quantitative significance of the latter was investigated by comparison with the known oxidant tert-butyl hydroperoxide (t-BOOH). At a concentration of 100 microM, t-BOOH caused an increase in the concentration of GSSG in BCNU-pretreated lung slices which was comparable to that after treatment with Co(II)/H2O2 or CO(II)/BCNU. None of these treatments resulted in a loss of protein thiols. Furthermore, in contrast to Co(II), t-BOOH/BCNU treatment did not result in impaired cell functions. However, at a t-BOOH concentration of 250 microM, t-BOOH/BCNU treatment caused a significantly greater increase in the level of GSSG than that caused by the previous treatments and was associated with both a loss of protein thiols and increased cell dysfunction. We have concluded from these data that under our experimental conditions, Co(II)-induced cell dysfunction is not a consequence of oxidation of cellular glutathione. The reason for this appears to be that the extent of glutathione oxidation by Co(II) even at a concentration which induces cell dysfunction is not of sufficient magnitude to result in the oxidation of protein thiol groups, an event which is likely to constitute the critical consequence of glutathione oxidation in the toxic process.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Lewis CP,Demedts M,Nemery Bdoi
10.1016/0006-2952(92)90573-2subject
Has Abstractpub_date
1992-02-04 00:00:00pages
519-25issue
3eissn
0006-2952issn
1873-2968pii
0006-2952(92)90573-2journal_volume
43pub_type
杂志文章abstract::Understanding the mechanisms of transport processes in the placenta can improve the safety and efficacy of drug delivery during pregnancy. Functional studies of organic cation transporters (OCTs) are usually carried out using radioactivity, and a fluorescent marker would add flexibility to experimental methods. As a p...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.11.020
更新日期:2007-03-15 00:00:00
abstract::The metabolism of tienilic acid, a drug containing a thiophene ring, was reinvestigated in man, rat and dog. The major urinary metabolite in man and rat was isolated and completely characterized by comparison with a synthetic compound. This metabolite derives from the hydroxylation of the thiophene ring of tienilic ac...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90409-x
更新日期:1984-05-01 00:00:00
abstract::Rat liver cells were separated into parenchymal cells (PC), Kupffer cells (KC) and endothelial cells (EC). The distribution of carboxylesterases (EC 3.1.1.1) between these cell types was investigated by PAGE and chromatogenic substrate staining, and compared with the results for total liver preparation and individual ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90423-g
更新日期:1992-08-18 00:00:00
abstract::Despite the steadily increased numbers of formyl peptide receptor (FPR) ligands identified over the years, few have been characterized in studies using animal disease models and even less have entered clinical trials in human subjects. A small-molecule compound, Act-389949, was however recently tested in a phase I cli...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2019.04.030
更新日期:2019-08-01 00:00:00
abstract::Two specific binding sites for histamine were characterized in the cell membrane of N-nitroso-N-methylurea (NMU)-induced tumors. The first one, with higher affinity (Kd = 4 +/- 2 nM), was further identified as an H2 type, while the lower affinity one (35 +/- 10 nM) corresponded to an H1 receptor. Histamine concentrati...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)00108-c
更新日期:1995-06-29 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::Three therapeutic inhibitors of vertebrate alpha-glucosidases recently assayed in research on diabetes control, show high inhibitory potencies towards the p-NP-alpha-D-glucosidase activity of honeybee haemolymph. BAYe 4609 is an allosteric V-type (pure non-competitive) inhibitor with: Ki congruent to K'i congruent to ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90131-9
更新日期:1982-09-01 00:00:00
abstract::The interaction of various cholecystokinin (CCK) peptides with the protein inhibitor (PK-I) of cyclic AMP dependent protein kinase (A-PK) has been studied. The order of the affinities (ED50) for relaxation of hog biliary muscle by a series of C-terminal peptides of CCK correlated with the order of the potencies for A-...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90578-6
更新日期:1983-03-01 00:00:00
abstract::Muscarinic receptors of the m2 subtype expressed in Chinese hamster ovary cells were labeled with [methyl-3H]acetylcholine([3H]ACh), and the rate of dissociation in the presence and absence of several compounds known to exert allosteric effects on labeled antagonist binding was observed. At 25 degrees C, [3H]ACh bound...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(96)00598-9
更新日期:1996-12-13 00:00:00
abstract::Rational approaches to targeted cancer therapy have begun to predominate the pipelines of oncology drug development. Our rapidly increasing understanding of the "wiring" of tumor cells and the vulnerabilities of such cells that can potentially be exploited through targeted treatments has opened up enormous opportuniti...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2010.03.001
更新日期:2010-09-01 00:00:00
abstract::The localization of the low-affinity adenosine binding protein adenotin-1 with respect to distribution in rat organs and subcellular compartments was investigated. Adenotin-1 was characterized by 5'-N-ethylcarboxamido[2,8-3H]adenosine ([3H]NECA) binding and Western blotting. Cytosolic as well as membrane fractions of ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00483-8
更新日期:1998-02-15 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::Developmental correlation of higher levels of estrogen binding by macromolecules in rat liver supernatant and of increases in plasma renin substrate levels after estrogen administration is reported. Gel filtration columns were used to separate bound from free radioactivity in studying binding of radioactive estradiol...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(77)90467-1
更新日期:1977-05-15 00:00:00
abstract::Poly(ADP-ribosylation) consists in the conversion of β-NAD(+) into ADP-ribose, which is then bound to acceptor proteins and further used to form polymers of variable length and structure. The correct turnover of poly(ADP-ribose) is ensured by the concerted action of poly(ADP-ribose) polymerase (PARP) and poly(ADP-ribo...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2010.04.022
更新日期:2010-12-15 00:00:00
abstract::Understanding the mechanism of resistance to tubulin-targeted anticancer drugs is important for improved chemotherapy. In this work, a colchicine-resistant MCF-7 cell line (MCF-7Col30) was generated by the gradual increment of colchicine treatment and the MCF-7Col30 showed ∼8-fold resistance towards colchicine. MCF-7C...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2017.02.018
更新日期:2017-05-15 00:00:00
abstract::Pioglitazone (PIO), a PPARγ agonist that improves glycemic control in type 2 diabetes through its insulin-sensitizing action, has been shown to exhibit beneficial effects in the vessel wall. For instance, it inhibits vascular smooth muscle cell (VSMC) proliferation, a major event in atherosclerosis and restenosis afte...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.11.026
更新日期:2016-02-01 00:00:00
abstract::The mechanisms of toxicity and sensitization by the radiosensitizer misonidazole [1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol] are not well understood. We report here on the inhibition of total glutathione peroxidase (GSHPx), selenium-dependent glutathione peroxidase (selenium-GSHPx) and glutathione transferase (GSH...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90399-0
更新日期:1986-09-15 00:00:00
abstract::The pregnane X-receptor (PXR) is a promiscuous nuclear receptor primarily responsible for the induction of genes from the cytochrome P450 3A family. In this study, we used a previously described PXR/SRC tethered protein to establish two in vitro assays for identifying PXR ligands: automated ligand identification syste...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.12.003
更新日期:2011-03-01 00:00:00
abstract::Protein kinase D (PKD) is a subfamily of serine/threonine specific family of kinases, comprised of PKD1, PKD2 and PKD3 (PKCμ, PKD2 and PKCv in humans). It is known that PKCs activate PKD, but the relative expression of isoforms of PKD or the specific PKC isoform/s responsible for its activation in platelets is not kno...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2011.06.032
更新日期:2011-10-01 00:00:00
abstract::The metabolism of mitozantrone, a chemotherapeutic agent used in the treatment of breast cancer, has been studied in vitro using rat liver subcellular fractions. This compound would appear to be metabolized by two interesting pathways. One involves conjugation with glucuronic acid, catalyzed most effectively by a 3-me...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90127-9
更新日期:1986-05-01 00:00:00
abstract::3-Morpholino-sydnonimine (SIN-1) is a NO-releasing compound which mimics the effects of cGMP through activation of soluble guanylyl cyclase. Its prodrug, molsidomine (SIN-10), does not release NO but does modulate various cell functions. These findings prompted us to study the effects of SIN-10 and SIN-1 on the respir...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90397-2
更新日期:1992-08-18 00:00:00
abstract::The thiopurine drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are well-established agents for the treatment of leukaemia but their main modes of action are controversial. Thiopurine methyltransferase (TPMT) metabolises thiopurine drugs and influences their cytotoxic activity. TPMT, like DNA methyltransferases ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.07.026
更新日期:2008-10-15 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::Phentermine was shown in the 1970s to inhibit the metabolism of serotonin by monoamine oxidase (MAO), but never was labeled as an MAO inhibitor; hence, it was widely used in combination with fenfluramine, and continues to be used, in violation of their labels, with other serotonin uptake blockers. We examined the effe...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00306-3
更新日期:2000-06-15 00:00:00
abstract::a synthetic seleno-organic compound, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one (PZ 51), exhibits GSH peroxidase-like activity in vitro, in contrast to its sulfur analog, PZ 25. In addition, PZ 51 behaves as an antioxidant shown by a temporary protection of rat liver microsomes against ascorbate/ADP-Fe-induced lipid per...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90083-2
更新日期:1984-10-15 00:00:00
abstract::Escape from the proper control of the cell cycle by up-regulation of cyclins or aberrant activation of cyclin-dependent kinases (CDKs) as well as by inactivation of cellular inhibitors of CDKs (CKI) leads to malignant transformation. Loss of cellular CKIs in cancers provided a rationale for development of pharmacologi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.07.040
更新日期:2008-12-01 00:00:00
abstract::Endotoxin (LPS) and interleukin-1 beta (IL-1 beta) increased the expression of tissue factor, a membrane-anchored glycoprotein that initiates blood coagulation on the surface of cultured human umbilical vein endothelial cells (HUVEC) and human monocyte/macrophages. On monocyte/macrophages, oleic acid strongly inhibite...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90118-x
更新日期:1994-07-19 00:00:00
abstract::The 5-HT1A receptor is a critical mediator of serotonergic (5-HT) function. We have identified 13 potential single nucleotide polymorphisms resulting in amino acid changes throughout the human 5-HT1A receptor. The pharmacological profiles of these 13 polymorphic variants were then characterized using a high-throughput...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2003.09.030
更新日期:2004-02-01 00:00:00
abstract::Inflammation, especially chronic inflammation, is directly involvement in the pathogenesis of many diseases including cancer. An effective approach for managing inflammation is to employ chemicals to block activation of nuclear factor-κB (NF-κB), a key regulator for inflammatory processes. Piperlongumine (piplartine, ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.03.014
更新日期:2015-06-01 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