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 carboxylase activity. This effect was mimicked by 8-Br-cGMP and abolished by KT5823, a selective inhibitor of cGMP-dependent protein kinase (PKG). Furthermore, specific and hydrolysis-resistant activators of PKG, and inhibitors of Ca2+ release from endoplasmic reticulum, were also effective in inhibiting both fatty acid-synthesizing activities. These results suggest that this biological action of NO is regulated by a signaling cascade involving soluble guanylyl cyclase, cGMP, and PKG, and may be mediated, at least in part, by inhibition of Ca2+ release from endoplasmic reticulum. In addition, 8-Br-cGMP was able to stimulate fatty acid oxidation by two different mechanisms: the relieving of malonyl-CoA-dependent inhibition by lowering levels of this product of acetyl-CoA carboxylase, and a malonyl-CoA-independent stimulation of carnitine palmitoyltransferase I. Taken together, results of this study suggest that NO/cGMP signaling pathway is endowed with regulatory properties in fatty acid metabolism, and may have a physiological role in the control of this metabolism in liver.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
García-Villafranca J,Guillén A,Castro Jdoi
10.1016/s0006-2952(02)01623-4subject
Has Abstractpub_date
2003-03-01 00:00:00pages
807-12issue
5eissn
0006-2952issn
1873-2968pii
S0006-2952(02)01623-4journal_volume
65pub_type
杂志文章abstract::Fundamental progresses have been made in pain research with a comprehensive understanding of the neuronal pathways which convey painful sensations from the periphery and viscera to the central nervous system and of the descending modulating pathways. Nevertheless, many patients still suffer from various painful condit...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2020.114397
更新日期:2020-12-28 00:00:00
abstract::Oxidative damage of creatine kinase (CK) induced by Adriamycin((R)) (ADM) with peroxidase was investigated using horseradish peroxidase (HRP). ADM oxidatively inactivated CK during its interaction with HRP in the presence of H(2)O(2) (HRP-H(2)O(2)). The red color of ADM was lost during oxidation by HRP-H(2)O(2). Addin...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00303-8
更新日期:2000-07-01 00:00:00
abstract::SR 4233 or WIN 59075 (3-amino-1,2,4-benzotriazine-1,4-dioxide) is a novel and highly selective hypoxic cell cytotoxin requiring reductive bioactivation for its impressive antitumour effects. Expression of appropriate reductases will contribute to therapeutic selectivity. Here we provide more detailed information on th...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90007-6
更新日期:1992-07-22 00:00:00
abstract::The first-generation histamine H1-receptor antagonists, chlorpheniramine (CPHE) and diphenhydramine (DPH), may activate histamine release from basophils and mast cells. Because CPHE and DPH are cationic-amphiphilic and because several substances with such physicochemical properties activate heterotrimeric regulatory g...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02123-x
更新日期:1996-01-26 00:00:00
abstract::[[trans-PtCl(NH(3))(2)](2)mu-(trans-Pt(NH(3))(2)(H(2)N(CH(2))(6)-NH(2))(2))](4+) (BBR3464) is a cationic trinuclear platinum drug that is being evaluated in phase II clinical trials for treatment of lung and ovarian cancers. The structure and DNA binding profile of BBR3464 is different from drugs commonly used clinica...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.12.016
更新日期:2007-05-01 00:00:00
abstract::Targeting of deregulated protein tyrosine kinases has been proposed as a new approach in the therapeutic intervention against pathological processes including proliferative disorders and cancer. Using a screening approach based on a comparative evaluation of antiproliferative effects in a panel of tumor cells with dif...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00278-1
更新日期:2000-06-15 00:00:00
abstract::The effect of 5 consecutive daily i.p. doses of CPZ (5 mg/kg), PZ (10 mg/kg) and PMZ (10 mg/kg) on the activity of kynurenine hydrolase and kynurenine aminotransferase in mouse liver was studied. All three phenothiazines effected an increase in the activity of kynurenine hydrolase per unit weight of liver with CPZ sho...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90105-8
更新日期:1982-07-01 00:00:00
abstract::Elongator, a multi-subunit complex assembled by the IkappaB kinase-associated protein (IKAP)/hELP1 scaffold protein is involved in transcriptional elongation in the nucleus as well as in tRNA modifications in the cytoplasm. However, the biological processes regulated by Elongator in human cells only start to be elucid...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.03.006
更新日期:2008-06-01 00:00:00
abstract::The mechanism of aerobic resistance to the quinone-containing anti-tumour agents mitomycin C (MMC) and porfiromycin (PM) has been investigated using non-transformed human cells. One of the cell strains used (3437T) was derived from an afflicted member of a cancer-prone family. This cell strain had been shown previousl...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90108-h
更新日期:1991-05-01 00:00:00
abstract::Nucleoside analogs conjugated with galactosyl-terminating peptides selectively enter liver cells and after intracellular release from the carrier partly exit into bloodstream, resulting in higher concentrations in liver blood than in systemic circulation. The aim of the present experiments was to ascertain whether, in...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00561-x
更新日期:2001-02-15 00:00:00
abstract::Pretreatment of NG108-15 cells with 0.03-25 microM prostaglandin E1 (PGE1) produced decreases in the maximal stimulation of adenylate cyclase activity produced by iloprost, N-ethylcarboxamidoadenosine and sodium fluoride. The rate of desensitization to all three agents was dependent on the concentration of PGE1 used, ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90405-7
更新日期:1994-03-15 00:00:00
abstract::Our previous work established that hypocholesterolemic agents altered K-ras intracellular localization in lung. Here, we examined K-ras activity to define further its potential importance in lung carcinogenesis. K-ras activity in lungs from male A/J, Swiss and C57BL/6 mice was examined. For 3 weeks, mice consumed eith...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.08.026
更新日期:2006-12-15 00:00:00
abstract::Activated blood platelets play crucial role in restenosis due to their fundamental significance in thrombus formation. Therefore, platelets are attractive targets for the inhibition with a variety of antagonists. In this study, we present direct evidence that GR144053F [non-peptide antagonist of glycoprotein IIb-IIIa ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00777-8
更新日期:2001-11-15 00:00:00
abstract::The population growth rate of HeLa cells treated with 60 microM 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) in reinforced Eagle's minimum essential medium was directly related to the concentration of fetal bovine serum in the range from 5 to 30%. Control cells proliferated at a maximal rate (doubling time: ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90306-x
更新日期:1984-02-15 00:00:00
abstract::The nuclear receptors liver X receptor (LXR) alpha and LXRbeta serve as oxysterol receptors and play an important role in the regulation of lipid metabolism. We investigated the potential effects of LXRs on pathways of colon carcinogenesis and found that LXR activation suppresses the transactivation activity of beta-c...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.10.007
更新日期:2009-01-15 00:00:00
abstract::The formation of triacylglycerols containing fenoprofen was studied in rat isolated adipocytes and hepatocytes incubated with [3H]glycerol and R or S fenoprofen. In both hepatocytes and adipocytes there was a high-affinity enzymatic process for the synthesis of triacylglycerol containing fenoprofen which was stereospe...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90537-0
更新日期:1988-05-15 00:00:00
abstract::Two radiolabelled derivatives of deferrioxamine B (DF) have been synthesized: methyl-DF and acetyl-DF. Both derivatives are non cytotoxic and stable in cell culture but they are degraded in human plasma and more extensively in rat plasma. Methyl-DF, acetyl-DF and DF mobilize radioiron to the same extent from hepatocyt...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90492-7
更新日期:1985-04-15 00:00:00
abstract::A 4',5'-unsaturated 5'-fluoroadenosine inhibitor of S-adenosyl-L-homocysteine hydrolase (SAH hydrolase; EC 3.3.1.1), MDL 28842, was found to inhibit markedly the growth of Plasmodium falciparum in vitro and Plasmodium berghei in mice. Inhibition of P. berghei growth was associated with a large increase in the concentr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90562-y
更新日期:1990-08-01 00:00:00
abstract::The development of an oxidant/antioxidant imbalance in lung inflammation may activate redox-sensitive transcription factors such as nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1), which regulate the genes for proinflammatory mediators and protective antioxidant genes. GSH, a ubiquitous tripeptide t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0006-2952(00)00392-0
更新日期:2000-10-15 00:00:00
abstract::Using the incorporation of [3H]isoleucine or [3H]hypoxanthine into acid-insoluble products as indices of protein- and nucleic acid-synthetic activity, respectively, it was shown that seven plant-derived quassinoids with differing chemical substitutions all inhibited protein synthesis more rapidly than nucleic acid syn...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90644-8
更新日期:1989-12-15 00:00:00
abstract::Psychedelic new psychoactive substances (NPS), compounds exerting their main pharmacological effects through the activation of the serotonin 2A receptor (5-HT2AR), continuously comprise a substantial portion of the reported NPS. However, these substances and their exact mechanism of action, differentiating them from n...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.114251
更新日期:2020-12-01 00:00:00
abstract::To study the effect of growth factors on iatrogenic apoptosis, we examined the influence of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) on staurosporine-induced apoptosis in primary cultures of human umbilical vein endothelial cells (HUVEC). Apoptosis was evaluated by a cell viability t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2003.09.007
更新日期:2004-01-15 00:00:00
abstract::To determine if both the Ca2+-calmodulin system and the cyclic AMP system may regulate tyrosine hydroxylase (TH) activity in situ, rat striatal tissue slices that contain all of the components of the TH, cyclic AMP and Ca2+-calmodulin systems were subjected to experimental manipulations. Incubation of striatal tissue ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90560-x
更新日期:1985-08-01 00:00:00
abstract::[Carboxyl-14C] labelled 1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (I) and 1-methyl-1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (II) were synthesized and their decarboxylation was studied in mouse brain homogenate and buffer. The decarboxylation rates of (I) and (II) in the homogenate were about 6-fol...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90173-5
更新日期:1986-08-15 00:00:00
abstract::During a cellular screening of thiocolchicine analogs, thiocolchicine dimers resulted particularly active in cisplatin-resistant A2780-CIS cells. In order to discover by which mechanism(s) thiocolchicine dimers overcame cisplatin resistance, p53, p21waf1 and MLH1 were assessed by Western blot. Results pointed out that...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.09.004
更新日期:2005-01-01 00:00:00
abstract::Andrographis paniculata has long been part of the traditional herbal medicine system in Asia and in Scandinavia. Andrographolide was isolated as a major bioactive constituent of A. paniculata in 1951, and since 1984, andrographolide and its analogs have been scrutinized with modern drug discovery approach for anti-inf...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2017.03.024
更新日期:2017-09-01 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 therapeutic efficacy of immunosuppressive agents has been intensively studied for colitis management. We synthesized a series of andrographolide derivatives and reported their structure-activity-relationship and anti-inflammatory activity in our previous studies. Among these derivatives, compound 3b exhibited the ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2019.03.019
更新日期:2019-05-01 00:00:00
abstract::The binding of [3H]nitrendipine to rat cortical membranes was reduced by phenytoin, phenobarbital, and pentobarbital. The IC50 values were 0.09, 0.40, and 0.76 mM respectively. The drugs reduced the apparent binding affinity of [3H]nitrendipine with little effect on the maximum number of binding sites. The inhibitory ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90416-2
更新日期:1985-06-15 00:00:00
abstract::Daunorubicin (DNR) is a well known anticancer drug believed to act mainly by topoisomerase II inhibition and mitochondria-mediated free radical generation. Though several studies were dedicated to elucidate the mechanism of action of DNR, however the mechanism still remains illusive. DNR is reported to affect mitochon...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.06.009
更新日期:2007-09-15 00:00:00