Abstract：
:Here we report that organic copper complexes can potently and selectively inhibit the chymotrypsin-like activity of the proteasome in vitro and in vivo. Several copper compounds, such as NCI-109268 and bis-8-hydroxyquinoline copper(II) [Cu(8-OHQ)(2)], can inhibit the chymotrypsin-like activity of purified 20S proteasome. In human leukemia cells, proteasome inhibition occurs within 15min after treatment, followed by apoptosis. Neither proteasome inhibition nor apoptosis occurs in non-transformed, immortalized human natural killer cells under the same treatment. Furthermore, proteasome inhibition and apoptosis induction were detected in prostate cancer cells treated with the ligand 8-OHQ alone following pre-treatment with copper(II) chloride. None of these events occurred in cells treated with copper(II) chloride alone, 8-OHQ alone (without growth in copper-enriched media), or nickel(II) chloride pre-treatment followed by 8-OHQ. Furthermore, we found that copper-mediated inhibition of purified 20S proteasome cannot be blocked by a reducing agent and that organic copper compounds do not generate hydrogen peroxide in the cells, suggesting that proteasome inhibition and apoptosis induction are not due to copper-mediated oxidative damage of proteins. Our results suggest that certain types of organic ligands could bind to tumor cellular copper, forming potent proteasome inhibitors and apoptosis inducers at copper concentrations found in tumor tissues.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Daniel KG,Gupta P,Harbach RH,Guida WC,Dou QPdoi
10.1016/j.bcp.2003.10.031subject
Has Abstractpub_date
2004-03-15 00:00:00pages
1139-51issue
6eissn
0006-2952issn
1873-2968pii
S0006295203008876journal_volume
67pub_type
杂志文章abstract：:Curcumin (diferuoylmethane), the yellow pigment in the rhizome of tumeric (Curcuma longa), an ingredient of curry spice, is known to exhibit a variety of pharmacological effects including antitumor, antiinflammatory, and antiinfectious activities. Although its precise mode of action remains elusive, curcumin has been ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00251-7
更新日期：1997-10-15 00:00:00
abstract：:Previous studies from this lab and others have demonstrated that nitric oxide (NO) in a concentration dependent manner, modulated neutrophil and leukemic cell survival. Subsequent studies delineated importance of iNOS in neutrophil differentiation and leukemic cell death. On the contrary, role of nNOS in survival of t...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2019.113779
更新日期：2020-06-01 00:00:00
abstract：:The rat CYP2B gene subfamily includes CYP2B1, CYP2B2 and CYP2B3. Translation of an alternatively spliced hepatic CYP2B2 mRNA would generate a CYP2B2 variant, CYP2B2v, having eight additional amino acid residues inserted between CYP2B2 positions 274 and 275. The presence of CYP2B3 and CYP2B2v in rat liver has yet to be...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00502-3
更新日期：1996-10-25 00:00:00
abstract：:When rat peritoneal leucocytes were incubated with carbon tetrachloride, a PLA2 was activated, eicosanoids were generated and lysosomal and cytoplasmic enzymes were released. The predominant eicosanoid generated was TXB2 with lesser amounts of PGE2, 6-keto PGF1 alpha and LTB4. Preincubation of the cells with two struc...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90693-8
更新日期：1985-05-01 00:00:00
abstract：:Multidrug resistance-associated protein 2 (Mrp2) is an ATP-dependent export pump that mediates the formation of bile-salt-independent bile flow. Disruption of the canalicular localization of Mrp2, without changes in its expression, is observed in chronic liver failure and is accompanied by oxidative stress. We reporte...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.09.016
更新日期：2011-01-01 00:00:00
abstract：:Quantitative RNase protection assays were performed to determine the levels of muscarinic receptor subtype (m1-m5) mRNAs in rat hippocampi. Results showed that the m1, m3, and m4 subtype mRNAs were expressed at relatively high levels, but the levels of the m2 and m5 subtype were very low. Three weeks following aspirat...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00074-9
更新日期：1997-05-09 00:00:00
abstract：:Several reports suggest that the antimalarial mode of action of quinoline drugs may differ in their mechanistic details. The malaria parasite Plasmodium falciparum was treated in culture with chloroquine, amodiaquine, quinine and mefloquine in a dose- and time-dependent fashion. After removal of the drug, the viabilit...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00878-4
更新日期：2002-02-01 00:00:00
abstract：:The structure-dependent aryl hydrocarbon (Ah) receptor agonist and antagonist activities of the following substituted flavones were investigated: flavone, 4'-methoxy-, 4'-amino-, 4'-chloro-, 4'-bromo-, 4'-nitro-, 4'-chloro-3'-nitro-, 3'-amino-4'-hydroxy-, 3',4'-dichloro-, and 4'-iodoflavone. The halogenated flavones e...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00063-9
更新日期：1996-04-26 00:00:00
abstract：:Homocysteine has been shown to increase glutathione levels in C3H/10T1/2 Cl 8 cells. The present paper confirms that this increase was specific for non-dividing cells. Several other thiols and disulfides, including cysteamine, mercaptoethanol and dithioerythritol, also increased glutathione, but the specificity for qu...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90046-n
更新日期：1990-02-01 00:00:00
abstract：:The N,O-sulfate of minoxidil (Mnx) is the active agent in producing the vasodilation and the hair-growth stimulating responses observed with Mnx treatment. In this report, Mnx sulfation activity was assayed in cytosol prepared from several normal human livers, and Mnx sulfation was shown to correlate significantly wit...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90489-8
更新日期：1990-09-01 00:00:00
abstract：:Ethyl 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA) is strongly hypoglycaemic in fasted normal and diabetic rats [H. P. O. Wolf, K. Eistetter and G. Ludwig, Diabetologia 22, 456 (1982)]. POCA was fed for 12 weeks to rats on a standard low-fat (3%) diet at levels of 0.05% and 0.2% to give daily intakes of abou...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90242-9
更新日期：1984-02-01 00:00:00
abstract：:The glycolipid alpha-galactosylceramide (alpha-GalCer), when presented on CD1 molecules by antigen presenting cells (APCs) to invariant NKT (iNKT cells), is a potent immunomodulator. Indoleamine 2,3-dioxygenase (IDO), an enzyme catalyzing the catabolism of L-tryptophan along the kynurenine pathway, is inducible in APC...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.07.001
更新日期：2008-09-15 00:00:00
abstract：:Poly (ADP-ribose) polymerases (PARPs) facilitate repairing of cancer cell DNA damage as a mean to promote cancer proliferation and metastasis. Inhibitors of PARPs which interfering DNA repair, in context of defects in other DNA repair mechanisms, can thus be potentially exploited to inhibit or even kill cancer cells. ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.02.015
更新日期：2016-05-01 00:00:00
abstract：:We tested the influence of IFNgamma on proteasome activity in parental Hep G2 cells that do not metabolize ethanol, as well as in recombinant Hep G2-derived cells that express either or both alcohol dehydrogenase (ADH) and cytochrome P4502E1 (CYP2E1). IFNgamma treatment increased proteasome activity in VL-17A (ADH(+),...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00252-1
更新日期：2003-09-01 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：:The source of urinary catecholamines and the mechanisms by which tyrosine administration raises these compounds were investigated in rats. Adrenalectomy blocked the tyrosine-induced rise in urinary epinephrine but not dopamine or norepinephrine. Following chemical sympathectomy with 6-hydroxydopamine (6-OHDA), the tyr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90578-0
更新日期：1982-11-15 00:00:00
abstract：:This mini-review addresses the effect of glycosylation and phosphorylation on the conformational alterations of the epidermal growth factor receptor (EGFR). Based on studies with full-length and truncated EGFRs, we propose a model to suggest that receptor-receptor self-association, which occurs in the truncated recept...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(00)00425-1
更新日期：2000-10-15 00:00:00
abstract：:The effects of thromboxane A2 (TXA2) on the proliferation of vascular smooth muscles cells (VSMC) were examined using primary cultures of VSMC from rat aorta. U46619, a stable TXA2 mimetic, stimulated DNA synthesis of VSMC only in the presence of insulin. The effect was concentration-dependent with a half-maximal effe...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90096-4
更新日期：1990-12-01 00:00:00
abstract：:We have investigated the ability of certain dietary flavonoids, known to exert beneficial effects on the central nervous system, to affect neuronal apoptosis. We used cerebellar granule cells undergoing apoptosis due to potassium deprivation in a serum-free medium in either the absence or presence of the flavonoids ge...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.10.005
更新日期：2010-03-01 00:00:00
abstract：:The cytotoxicity of paracetamol and of its putative toxic metabolite, N-acetyl-p-benzo-quinoneimine (NABQI) have been investigated in hepatocytes from hamster, mouse, rat and human liver. Whereas paracetamol readily caused cell blebbing and a loss of viability in hepatocytes from mouse and hamster, human and rat hepat...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90412-6
更新日期：1987-04-01 00:00:00
abstract：:The alkanes, ethane and pentane, are often used as indices of lipid peroxidation. Because it has been indicated that O2 tension can affect the yield of these compounds, a systematic study of this was carried out. Rat liver microsomes were peroxidized using an iron-ascorbate system. The incubations were carried out in ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90186-9
更新日期：1987-03-15 00:00:00
abstract：:The effects of thiamine thiazolone (TT) and thiamine thiazolone pyrophosphate (TTPP) on the in vitro and in vivo inhibition of pyruvate dehydrogenase complex (PDHC) from rat cortex and hippocampus were characterized. TTPP decreased PDHC activity in vitro but had no effect in vivo following its direct chronic administr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90620-x
更新日期：1988-11-15 00:00:00
abstract：:Cucurbitacin E has been identified by an empiric screening strategy as a sterol with potent growth inhibitory activity in vitro directed against prostate carcinoma explants (IC50 of 7-50 nM in 2- to 6-day exposures). The mechanism of cucurbitacin cytoxicity has not been elucidated previously. In the present study, we ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(96)00557-6
更新日期：1996-11-22 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：: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：:Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays an important role in the cardiovascular system. However, the potential protective role of inhibitor 1 of protein phosphatase 1 (I1PP1), which is able to regulate CaMKII, in high glucose-induced cardiomyocytes injury remains unknown. In the present study, cardi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2019.02.022
更新日期：2019-05-01 00:00:00
abstract：:Glucuronidation of quinols of polycyclic aromatic hydrocarbons (PAHs) represents an important detoxication pathway preventing toxic quinone/quinol redox cycles. Therefore, mono- and diglucuronide formation of benzo(a)pyrene-3,6-quinol was investigated and compared to that of structurally related 3,6-dihydroxychrysene ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00095-h
更新日期：1995-05-26 00:00:00
abstract：:PI3K cascade is a central signaling pathway regulating cell proliferation, growth, differentiation, and survival. Tight regulation of the PI3K signaling pathway is necessary to avoid aberrant cell proliferation and cancer development. Together with SHIP-1, the inositol phosphatases PTEN and SHIP-2 are the gatekeepers ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2011.05.031
更新日期：2011-11-15 00:00:00
abstract：:Metabolomics offers the opportunity to uncover endogenous biomarkers that can lead to metabolic pathways and networks and that underpin drug toxicity mechanisms. A novel protocol is presented and discussed that is applicable to drugs which generate urinary metabolites when administered to mice sensitive to its toxicit...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2018.09.022
更新日期：2018-10-01 00:00:00
abstract：:The carrier protein for methotrexate and tetrahydrofolate cofactors (GP-MTX) in CCRF-CEM human lymphoblastic leukemia cells in a 117 kDa glycoprotein containing both N- and O-linked oligosaccharides (Matherly et al., J Biol Chem 267: 23253-23260, 1992). Tunicamycin, an inhibitor of N-glycosylation, was used to investi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90423-5
更新日期：1994-03-15 00:00:00
