Abstract：
:In a variety of malignant cells the prostate-apoptosis-response-gene-4 (Par-4) induces increased sensitivity towards chemotherapeutic agents by down-regulating anti-apoptotic B-cell lymphoma-gene 2 (Bcl-2). Hypothesizing that Par-4 also influences apoptosis in myeloid cell lines, we tested this hypothesis by stably transfecting bcr-abl transformed-K562 cells with a Par-4-expressing vector. Here we demonstrate that over-expression of Par-4 in K562 cells up-regulates expression levels of Bcl-2 and death-associated protein (Daxx). Upon treatment with different chemotherapeutic agents, Fas- or TRAIL agonistic antibodies, Par-4-positive cells did not exhibit an increased rate of apoptosis as compared to Par-4-negative control cells. However, incubation with histone deacetylase (HDAC)-inhibitors Trichostatin A (TSA) and LAQ824 or the tyrosinkinase inhibitor Imatinib (STI571) increased the rate of apoptosis in Par-4-positive K562 cells. Assessing the underlying molecular mechanisms for the Par-4-induced response to HDAC-inhibitors and STI571 we provide evidence, that these effects are associated with a down-regulation of Daxx, enforced activation of caspases and enhanced cleavage of cellular inhibitor of apoptosis (cIAP)-1 and -2.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Brieger A,Boehrer S,Schaaf S,Nowak D,Ruthardt M,Kim SZ,Atadja P,Hoelzer D,Mitrou PS,Weidmann E,Chow KUdoi
10.1016/j.bcp.2004.02.028subject
Has Abstractpub_date
2004-07-01 00:00:00pages
85-93issue
1eissn
0006-2952issn
1873-2968pii
S0006295204001534journal_volume
68pub_type
杂志文章abstract：:The prevalence of hyperuricemia/gout increases with aging. However, the effect of aging on function for excretion of uric acid to out of the body has not been clarified. We found that ileal uric acid clearance in middle-aged rats (11-12 months) was decreased compared with that in young rats (2 months). In middle-aged ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2015.06.021
更新日期：2015-09-01 00:00:00
abstract：:During the molecular transduction of itch, the stimulation of pruriceptors on sensory fibers leads to the activation or sensitization of ion channels, which results in a consequent depolarization of the neurons. These ion channels mostly belong to the transient receptor potential (TRP) channels, which are involved in ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.114310
更新日期：2021-01-01 00:00:00
abstract：:Pancreatic stellate cells (PSCs) play a key role in pancreatic fibrosis, a constant feature of chronic pancreatitis. PSC activation occurs in response to profibrogenic mediators such as cytokines and involves proliferation, transition towards a myofibroblastic phenotype and enhanced production of extracellular matrix ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00075-3
更新日期：2003-04-15 00:00:00
abstract：:Boldine ([S]-2,9-dihydroxy-1,10-dimethoxyaporphine) has been shown to exert antioxidant and anti-inflammatory effects. The present study elucidated the protective effect of boldine on catecholamine-induced membrane permeability transition in brain mitochondria and viability loss in PC12 cells. Dopamine (200 microM) an...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00852-8
更新日期：2002-02-01 00:00:00
abstract：:The aim of the present study was to estimate the relative contribution of rat P450 isoforms to the metabolism of caffeine and to assess the usefulness of caffeine as a marker substance for estimating the activity of P450 in rat liver and its potential for pharmacokinetic interactions in pharmacological experiments. Th...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.12.017
更新日期：2008-04-01 00:00:00
abstract：:The interaction of the anti-tumor anthraquinones, ametantrone and mitoxantrone, with rat hepatic microsomes has been studied with a fluorescence technique using 7,12-dimethylbenzanthracene as a new fluorescent probe. The two drugs were able to quench the intrinsic fluorescence of microsomal suspension. Mitoxantrone wa...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90059-7
更新日期：1988-10-15 00:00:00
abstract：:Purification of functional nucleoside transporters has been hampered by the instability of detergent-solubilized proteins. The present study was undertaken to determine if the presence of specific transporter ligands in the solubilization medium could enhance the functional stability of the isolated proteins. Ehrlich ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(96)00857-x
更新日期：1997-03-07 00:00:00
abstract：:Sulfasalazine (SF) promotes remyelination and improves the outcome of multiple sclerosis (MS) patients. However, the underlining mechanism remains elusive. Here, we examined whether SF blocks microglia switching to a pro-inflammatory M1-like phenotype through a competing endogenous RNA (ceRNA) effects in cuprizone-ind...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.06.028
更新日期：2018-09-01 00:00:00
abstract：:The effects of physiological and pathological concentrations of glucocorticoids were investigated using the glucocorticoid antagonist RU486 and the synthetic glucocorticoid dexamethasone, respectively. The effects of these treatments on the concentrations of glutamine and other amino acids in skeletal muscle and plasm...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90505-f
更新日期：1990-09-01 00:00:00
abstract：:A serine peptidase (RLK1) was partially purified from rat liver homogenates. Its molecular weight was 80,000, and its optimum pH was 7.5. Bz-Tyr-O-Et was hydrolyzed by the enzyme, which was inhibited by Ip2PF, PMSF and by Tos-Phe-CH2Cl. The bonds cleaved by the enzyme were Phe5-Ser6 and Phe8-Arg9, when bradykinin was ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90466-x
更新日期：1982-03-01 00:00:00
abstract：:Several drug compounds have failed in clinical trials due to extensive biotransformation by aldehyde oxidase (AOX) (EC 1.2.3.1). One of the main reasons is the difficulty in scaling clearance for drugs metabolised by AOX, from preclinical species to human. Using methotrexate as a probe substrate, we evaluated AOX meta...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2015.05.010
更新日期：2015-08-01 00:00:00
abstract：:The effects of 3-monoalkyl- and 3,5-dialkyl-substitution on the cytotoxicity of paracetamol (PAR) in rat hepatocytes was studied. PAR is known to be bioactivated by the hepatic microsomal cytochrome P-450 containing a mixed-function oxidase system presumably to N-acetyl-para-benzoquinone imine (NAPQI), a reactive meta...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90653-2
更新日期：1986-11-01 00:00:00
abstract：:H460 non-small cell lung, HCT116 colon and 4T1 breast tumor cell lines induced into senescence by exposure to either etoposide or doxorubicin were able to recover proliferative capacity both in mass culture and when enriched for the senescence-like phenotype by flow cytometry (based on β-galactosidase staining and cel...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.12.013
更新日期：2019-04-01 00:00:00
abstract：:We hypothesized that the histamine H(3)-receptor (H(3)R)-mediated attenuation of norepinephrine (NE) exocytosis from cardiac sympathetic nerves results not only from a Galpha(i)-mediated inhibition of the adenylyl cyclase-cAMP-PKA pathway, but also from a Gbetagamma(i)-mediated activation of the MAPK-PLA(2) cascade, c...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.01.001
更新日期：2007-04-15 00:00:00
abstract：:Raf kinase inhibitor protein (RKIP) is a member of the phosphatidylethanolamine-binding protein (PEBP) family. RKIP plays a pivotal modulatory role in several protein kinase signaling cascades. RKIP binds inhibits Raf-1-mediated phosphorylation of MEK through binding to Raf-1. Protein kinase C (PKC) phosphorylates RKI...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2004.04.024
更新日期：2004-09-15 00:00:00
abstract：:The effect of loxoprofen-Na, a novel non-steroidal anti-inflammatory drug with a prodrug property, on prostaglandin (PG) levels in the inflammatory tissue was investigated with a carrageenin-induced pleurisy model in rats. The intrapleural injection of carrageenin caused a marked increase in the levels of PGE2 and 6-k...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90242-w
更新日期：1991-11-27 00:00:00
abstract：:Glucocorticoids (GCs) are steroid hormones widely used as coadjuvants in the treatment of solid tumors due to their anti-inflammatory effects. However, evidence show that they also may induce chemotherapy resistance, probably through their capacity to inhibit apoptosis triggered by antineoplastic drugs. GCs exert thei...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.04.006
更新日期：2014-06-15 00:00:00
abstract：:Partial agonists for G protein-coupled receptors (GPCRs) provide opportunities for novel pharmacotherapies with enhanced on-target safety compared to full agonists. For the human adenosine A1 receptor (hA1AR) this has led to the discovery of capadenoson, which has been in phase IIa clinical trials for heart failure. A...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.114144
更新日期：2020-10-01 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：:The inhibitory effect of a range of nitroimidazole-derivatives on H2 production by metronidazole resistant (CDC-85) and susceptible (C1-NIH) Trichomonas vaginalis strains was investigated. The 2-, 4-, and 5-nitro-derivatives used had one-electron reduction potentials within the range -250 to -525 mV. Nitroimidazole co...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90327-8
更新日期：1986-05-15 00:00:00
abstract：:Oleanolic acid (OA) is a natural triperpenoid that protects against a variety of hepatotoxicants such as carbon tetrachloride, cadmium, acetaminophen, and bromobenzene. To gain insight into the molecular mechanisms of this generalized hepatoprotection, genomic analysis was performed on mouse and rat livers after OA tr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.07.021
更新日期：2008-10-01 00:00:00
abstract：:Carboxylesterases (CESs) play important roles in the metabolism of many ester-drugs. In the present study, we identified and characterized dexamethasone-induced methylprednisolone hemisuccinate (MPHS) hydrolase in rat liver microsomes. Intraperitoneal injection of dexamethasone resulted in a significant increase in th...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.01.017
更新日期：2005-04-15 00:00:00
abstract：:Endosulfan (E) is an organochloric insecticide, which is quickly metabolized and eliminated from the body system. Toxic effects of E and its metabolites have been reported. The influence of E and its metabolites, viz. endosulfan sulfate (ES), endosulfan diol (ED) and endosulfan lactone (EL), has been examined on rat l...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90112-6
更新日期：1984-11-01 00:00:00
abstract：:Adenosine triphosphate (ATP) is a molecule that on one hand plays a central role in cellular energetics and which on the other is a ubiquitous signaling molecule when released into the extracellular media. Extracellular ATP accumulates in inflammatory environments where it acts as a damage-associated molecular pattern...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2020.114385
更新日期：2020-12-20 00:00:00
abstract：:Naphthoquinone derivatives and metabolites are widely dispersed molecules in nature. Alkannin, a natural naphthoquinone compound, induces excellent cytotoxicity in cancer cells. However, the detailed mechanism by which alkannin inhibits cancer cell survival remains unclear. In the present study, we isolated alkannin f...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.114167
更新日期：2020-10-01 00:00:00
abstract：:Relatively low concentrations of ascorbic acid inhibited the binding of the alpha-1 adrenergic antagonist [125I]HEAT [DL-[beta(3-iodo-4-hydroxyphenyl)-ethyl-aminomethyl]-tetralone) in rat submandibular gland and rat aorta. However, no inhibition was observed with this ligand in several other tissues, nor with several ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90353-9
更新日期：1986-02-15 00:00:00
abstract：:Nitric oxide sensitive guanylyl cyclase (NOsGC) is a heterodimeric enzyme consisting of an α and a β subunit. Two heterodimeric enzymes are known to be important for NO-signalling in humans: α(1)/β(1) and α(2)/β(1). No difference had so far been detected with respect to their pharmacological properties, but as we show...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.08.007
更新日期：2010-12-01 00:00:00
abstract：:The Na+/K(+)-pump activity and the utilization of adenosine triphosphate (ATP) were studied in rat peritoneal mast cells after histamine secretion induced by compound 48/80. We measured the ouabain-sensitive K(+)-uptake by a radioactive technique (86Rb+). The ATP content and the glycolytic ATP-production were measured...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90299-2
更新日期：1994-05-18 00:00:00
abstract：:Autophagy is generally regarded as a mechanism to promote cell survival. However, autophagy can occasionally be the mechanism responsible of cell demise. We have found that a concomitant depletion of glucose, nutrients and growth factors provoked cell death in a variety of cell lines. This death process was contingent...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2015.09.021
更新日期：2015-12-15 00:00:00
abstract：:We have studied the effects of TPA on the metabolism of porcine thyroid cells cultured for 1-4 days in the absence (control cells) and in the presence of 0.1 mU/ml TSH (TSH cells). The phospholipid turnover, evaluated after a 2 hr incorporation of 32P-phosphate into phospholipids, is markedly modified by the presence ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90427-7
更新日期：1985-11-01 00:00:00
