Abstract:
:Hepcidin peptide is crucial in the regulation of systemic iron availability controlling its uptake from the diet and its release from the body storage tissues. Hepcidin dysregulation causes different human disorders ranging from iron overload (e.g. hemochromatosis) to iron deficiency (e.g. anemia). Hepcidin excess is common in the Anemia of Chronic Diseases or Anemia of Inflammation and in the genetic form of anemia named IRIDA; the pharmacological downregulation of hepcidin in these disorders could improve the anemia. Commercial heparins were shown to be strong inhibitors of hepcidin expression, by interfering with BMP6/SMAD pathway. The non-anti-coagulant heparins, modified to abolish the anti-thrombin binding site, were equally potent and could be used to improve iron status. To perform its anti-hepcidin activity heparin needs 2O- and 6O-sulfation and an average molecular weight (MW) up to 4000-8000 Dalton, depending on the sulfation level. The pentosane polysulfate (PPS), which shares with heparin a high degree of sulfation, is a compound with low anti-coagulant activity that is already in use for pharmaceutical treatment. In the present work we analyzed the anti-hepcidin activity of PPS in vitro and in vivo. We found that it acts as a strong inhibitor of hepcidin expression in HepG2 cells with an effect already visible after 2-3 h of treatment. It also suppressed hepcidin in mice in a dose dependent manner after 3 h and with a significant redistribution of systemic iron without evident side effects. PPS is also able to abolish the LPS dependent hepcidin upregulation similarly to that showed for heparin derivatives. These results suggest PPS as an interesting compound to control hepcidin in vivo.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Asperti M,Denardo A,Gryzik M,Castagna A,Girelli D,Naggi A,Arosio P,Poli Mdoi
10.1016/j.bcp.2020.113867subject
Has Abstractpub_date
2020-05-01 00:00:00pages
113867eissn
0006-2952issn
1873-2968pii
S0006-2952(20)30095-2journal_volume
175pub_type
杂志文章abstract::Cytidine deaminase, an enzyme found in the supernatant fluid of hepatocytes, granulocytes and tumor cells, and in plasma, degrades the antitumor agents cytosine arabinoside and 5-azacytidine. Uridine and its analogs, 3-deazauridine, 5-bromodeoxyuridine, 5-fluorodeoxyuridine and 6-azauridine, were found to competitivel...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(80)90561-4
更新日期:1980-03-01 00:00:00
abstract::Purinergic stimulation of surfactant secretion via exocytosis of lamellar bodies is mediated by an elevation of the intracellular Ca2+ concentration ([Ca2+](i)). We tested the dihydropyridine (DHP) analogues isradipine (+/-enantiomers), nifedipine and Bay K 8644 (racemic forms) on ATP-induced surfactant secretion and ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00582-2
更新日期:2001-05-01 00:00:00
abstract::3H-(+/-) propranolol and 125I-(+/-) cyanopindolol have been used to characterize beta adrenoceptors of liver, lung, kidney and heart of rat. Two main binding parameters, KD and Bmax were measured using either cells, homogenates or plasma membranes of each organ (except heart). Results show that the most accurate deter...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90365-9
更新日期:1983-11-15 00:00:00
abstract::Bronchial epithelial cells play an important role in amplifying and perpetuating airway inflammation and may be a target for inhaled steroids. We have characterized glucocorticoid receptors in primary human bronchial epithelial cells. Northern and western blot analyses demonstrated the expression of glucocorticoid rec...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00008-8
更新日期:1999-05-01 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::We have shown previously that (R)-5-fluoro-5,6-dihydrouracil (FUraH(2)) attenuates the antitumor activity of 5-fluorouracil (FUra) in rats bearing advanced colorectal carcinoma. Presently, we found that alpha-fluoro-beta-alanine (FBAL), the predominant catabolite of FUra that is formed rapidly via FUraH(2), also decre...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00408-6
更新日期:2000-04-15 00:00:00
abstract::In this paper, we illustrate how a proteomic analysis can be useful to approach complex biological problems, in this case the concept of stress-induced premature senescence (SIPS). According to the stochastic theories of ageing, damage that accumulate with time in the cellular components are responsible for cellular a...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0006-2952(02)01171-1
更新日期:2002-09-01 00:00:00
abstract::Accumulation of radioactive iron (59Fe) into isolated fragments of rat small intestine in the presence of two hydroxypyrones, maltol and ethyl maltol, was compared with that in the presence of another chelator of iron(III), nitrilotriacetic acid (NTA). The characteristics of uptake were similar with all three ligands....
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90556-4
更新日期:1988-05-15 00:00:00
abstract::Nuclear factor-kappaB (NF-kappaB) activity affects cell survival and determines the sensitivity of cancer cells to cytotoxic agents as well as to ionizing radiation. Preventing the protective function of NF-kappaB may result in chemo- and radio-sensitization of cancer cells. Therefore, NF-kappaB has emerged as one of ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0006-2952(98)00224-x
更新日期:1999-01-01 00:00:00
abstract::Ectonucleotidases are key for purinergic signaling. They control the duration of activity of purinergic receptor agonists. At the same time, they produce hydrolysis products as additional ligands of purinergic receptors. Due to the considerable diversity of enzymes, purinergic receptor ligands and purinergic receptors...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2020.114322
更新日期:2020-11-06 00:00:00
abstract::LLC-PK(1) is a proximal tubular cell line derived from normal pig kidney which has a structure and function similar to those of renal proximal tubular cells and which expresses baseline levels of P-glycoprotein. We isolated by drug selection a doxorubicin-resistant cell line (LLC-PK(1)/ADR) that exhibited a multidrug-...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00535-9
更新日期:2001-01-01 00:00:00
abstract::We report here studies on the regulation of the metabolism of adenosine 3',5'-monophosphate (cAMP) in established and primary cultures of rat pulmonary microvascular endothelial cells (RPMVEC). Inhibition by rolipram, a selective inhibitor of cAMP phosphodiesterase (PDE) of the PDE4 gene family, was required to achiev...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00914-5
更新日期:2002-02-15 00:00:00
abstract::Augmented endothelium-dependent contractions (EDC) contributes to endothelial dysfunction and vascular disease progression. An early signal in EDC is cytosolic [Ca2+]i rise in endothelial cells, which stimulates the production of contractile prostanoids, leading to vascular contraction. In this study, the molecular id...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.11.002
更新日期:2019-01-01 00:00:00
abstract::This report characterizes the cytochrome P-450 isozyme involved in midazolam metabolism. This study was undertaken into liver microsomal fractions prepared from untreated rabbits or animals treated with drugs known to specifically induce various cytochrome P-450 isozymes such as form LM2 by phenobarbital, LM4 and LM6 ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90541-2
更新日期:1988-05-15 00:00:00
abstract::Ciprofibrate (CP), a peroxisome proliferator, has been shown to reduce rat liver endoplasmic reticulum (ER) Ca(2+)-ATPase activity both in vitro and in vivo. The ER Ca(2+)-ATPase is highly susceptible to thiol reactivity, and maintenance of maximal enzyme activity is critically dependent upon the integrity of these th...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90021-n
更新日期:1993-05-25 00:00:00
abstract::Previous studies of platinum(II) compounds with bidentate leaving ligands have emphasized the contrast between the stability of the bidentate leaving ligand in vitro (T1/2 greater than 11 days in water) and the apparent reactivity of these bidentate platinum compounds in vivo. However, none of these studies actually m...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90646-6
更新日期:1988-09-01 00:00:00
abstract::The capabilities of 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3), and two novel vitamin D analogues, EB1089 and KH1060, to induce the differentiation of two established leukaemia cell lines, U937 and HL-60, were assessed alone or in combination with the retinoid compounds, 9-cis retinoic acid (9-cis RA) and all-trans ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00195-0
更新日期:1997-09-01 00:00:00
abstract:UNLABELLED:ZD1839 ("Iressa"), a selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is currently undergoing preclinical and clinical evaluation in several solid tumors. The present study aimed to assess the effect of ZD1839 in combination with oxaliplatin in the colon cancer cell lines HT-2...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00291-0
更新日期:2003-08-15 00:00:00
abstract::The in vitro inhibition of the cytochrome P-450 (P-450) isozyme specific positional hydroxylation of androst-4-ene-3,17-dione (androstenedione) by the alkylamino containing compounds trans- and cis-tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen, SKF 525-A and the non-alkylamino containing compounds tamoxifen meta...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90168-8
更新日期:1989-01-01 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::A calcium antagonist, verapamil, enhanced the cellular uptake and cytotoxicity of vincristine (VCR) in adriamycin-resistant P388 leukemia (P388/ADM) cells and also enhanced the cellular uptake and cytotoxicity of adriamycin (ADM) in vincristine-resistant P388 leukemia (P388/VCR) and P388/ADM cells. The enhancement of ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90097-1
更新日期:1982-10-01 00:00:00
abstract::The insulin receptor (IR) is composed of two alpha-chains that bind ligands and two beta-chains that possess an intracellular tyrosine kinase activity. The IR is expressed in cells as two isoforms containing or not exon 11 (IRB and IRA, respectively). Several mRNA studies have demonstrated that the two isoforms are co...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.07.027
更新日期:2008-10-01 00:00:00
abstract::The expression of drug resistance-associated mdr-1, GST pi, and topoisomerase II genes was analyzed in cell cycle phase enriched populations of doxorubicin-resistant murine leukemic P388/R-84 cells. Flow cytometric analysis of bromodeoxyuridine (BrdU) incorporation and staining with anti-BrdU antibodies was used to co...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)00443-p
更新日期:1995-02-14 00:00:00
abstract::Stroke is a neurological condition and may cause changes in hepatic drug-metabolizing enzymes. Hepatic CYP2B is involved in the metabolism of a variety of centrally active substances. The purpose of this study was to investigate the possible down-regulation mechanism of hepatic CYP2B after acute stroke. Using a rat mo...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.12.011
更新日期:2014-02-15 00:00:00
abstract::Here we report on the induction of resistance to photodynamic therapy (PDT) in the ABCG2-high human breast cancer cell line MA11 after repetitive PDT, using either Pheophorbide A (PhA) or di-sulphonated meso-tetraphenylchlorin (TPCS2a) as photosensitizer. Resistance to PhA-PDT was associated with enhanced expression o...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2017.08.002
更新日期:2017-11-15 00:00:00
abstract::Tanshinone I (Tanshinone-1), a major active principle of the traditional Chinese medicine Salvia miltiorrhiza, possesses excellent anticancer properties, including inhibiting proliferation, angiogenesis and metastasis and overcoming multidrug resistance (MDR). However, its direct anticancer molecular target(s) remain ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.05.006
更新日期:2018-08-01 00:00:00
abstract::The role of Ca2+ and protein kinase C (PKC) activity in the release of immunoreactive endothelin-1 (ET-1) from cultured porcine aortic endothelial cells of first or second passage has been studied. ET-1 accumulation within cells and secretion into cell-conditioned medium over 3 and/or 5 hr was measured. Confluent cell...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)00023-s
更新日期:1995-06-16 00:00:00
abstract::Only very low levels of peroxidase activity were detected in castrated male hamster kidneys [1.0 +/- 0.8(S.E.) units/g protein], and chronic estrogen administration, either diethylstilbestrol (DES) or 17 beta-estradiol, for 1-5 months did not result in any appreciable increase in this activity. In contrast, hamster li...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90529-4
更新日期:1983-02-01 00:00:00
abstract::Neuronal nicotinic acetylcholine receptors (nAChR), recognized targets for drug development in cognitive and neuro-degenerative disorders, are allosteric proteins with dynamic interconversions between multiple functional states. Activation of the nAChR ion channel is primarily controlled by the binding of ligands (ago...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2011.05.001
更新日期:2011-10-15 00:00:00
abstract::The present study was carried out to analyze the sex differences in the retention of Cd in rats treated with a small amount of Cd, and its mechanisms. Cd and Zn concentrations in the kidney and liver of female rats treated with 28 nmol Cd or 1 nmole Zn were significantly higher than those in male rats. Pretreatment wi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90305-x
更新日期:1988-08-15 00:00:00