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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The review of the contemporary state of bioinorganic chemistry is presented, illustrated by a series of examples. A short presentation of the chemistry of the complexes of transient metals is given, the importance of the distorsion isomerism is emphasized. The roles of the alkaline and alkaline-earth metals in biology is considered as also the role of Zn, Co, Mo, Cu. The function of iron is presented and the influence of magnetic fields on organisms is discussed. The mechanisms of action of carboxypeptidase A and of nitrogenase are considered. The general properties of metalloenzymes are discussed--the entatic state of the active site, the role of the distorsion isomerism and of the trans-effect as also the electronic-conformational interactions. The physical properties of the biometallic compounds are formulated. The importance of these compounds for medicine is illustrated by the Podymov's theory of lupus, by the cancerogenic role of metals and by the use of the platinum complexes in oncological therapy. The importance of biometallic compounds for enzymology and other branches of molecular biology is emphasized.
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PMID:[Bioinorganic chemistry and molecular biology]. 675 21

Bone marrow mast cell content was evaluated by a semiquantitative method in 22 marrow specimens from 20 patients with preleukemic syndrome and was compared with 21 marrow specimens from iron-deficient control subjects. Results indicate a statistically significant increase of bone marrow mast cell content in patients with preleukemic syndrome in comparison to control subjects (p less than or equal to 0.0005). Two of 20 preleukemic patients converted to acute myeloblastic leukemia and conversion was accompanied by a significant decrease of bone marrow mast cell content. Our findings indicate that bone marrow mast cell content can be reproducibly quantitated and represents an additional morphologic criterion for diagnosis of the preleukemic syndrome.
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PMID:Bone marrow mast cell content in preleukemic syndrome. 695 49

The nuclear DNA-binding protein NF-E2 is thought to mediate the powerful erythroid enhancer activity of the alpha- and beta-globin locus control regions and participates in the control of genes encoding two enzymes of haem biosynthesis (porphobilinogen deaminase and ferrochelatase). The major component of NF-E2 is a 45K polypeptide (designated p45 NF-E2) that belongs to the basic region-leucine zipper family of transcription factors. This subunit of NF-E2 is specifically expressed in haematopoietic progenitor cells and differentiated cells of the erythroid, megakaryocyte and mast cell lineages. The gene encoding p45 NF-E2 (murine gene Nfe2) has been mapped to mouse chromosome 15 near the mutation microcytosis (mk). Homozygous mk mice have severe hypochromic microcytic anaemia as a result of decreased globin synthesis and defects in intestinal and erythroid iron absorption. Here we investigate whether the mk mutation lies within Nfe2 by characterizing the p45 NF-E2 gene and determining its DNA sequence in wild-type and mk alleles. The mk allele carries a missense mutation that causes substitution of valine by alanine at amino acid 173 of the p45 NF-E2 protein. Expression of p45 NF-E2 messenger RNA was detected in erythroid tissues of normal mice and in the duodenum of normal and severely anaemic beta-thalassaemic (Hbbd-th3/Hbbd-th3) mice. We propose that the mk mutation results in an impaired form of NF-E2 which fails to regulate both globin production and iron metabolism properly.
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PMID:Mouse microcytic anaemia caused by a defect in the gene encoding the globin enhancer-binding protein NF-E2. 846 89

To test the hypothesis that allergy to desferrioxamine is not an immunologic mechanism, but arises from a local effect on the dermal mast cell, we have treated four patients who were not receiving chelation therapy because of hypersensitivity to standard subcutaneous (SC) therapy, with high-dose desferrioxamine (DFO) by the intravenous (IV) route. Three patients had central venous access ports implanted on the anterior chest wall. The fourth patient had the therapy delivered by the peripheral vein route. All patients had the drug delivered via an elastomeric infusor. Intravenous therapy was successful for all patients. During one year of therapy no local or systemic allergic manifestations were noted. In addition, no impairment of hearing or vision or any catheter complications were reported. A very high level of patient compliance to the therapy resulted in dramatically decreased iron stores and ferritin levels (2,759 ng/ml to 717.5 ng/ml) and a significant improvement in the clinical status of all patients. The absence of allergic episodes in this patient group after 1 year of i.v. therapy would strongly support the hypothesis that SC DFO allergy is related to a direct effect on dermal mast cells and is not an immunological reaction. This study suggests that patients with severe allergy to SC DFO can therefore safely receive their chelation therapy via the i.v. route.
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PMID:High-dose intravenous desferrioxamine (DFO) delivery in four thalassemic patients allergic to subcutaneous DFO administration. 857 45

We evaluated the role of basal nitric oxide (NO) release in the regulation of microvessel permeability under resting conditions. We measured changes in microvessel hydraulic conductivity (Lp) and endothelial cytoplasmic calcium concentration ([Ca2+]i) after application of NO synthase (NOS) inhibitors to the lumen of individually perfused frog mesenteric venular microvessels. NOS inhibitors caused a transient increase in Lp. The mean ratios of peak test Lp values relative to control values in the presence of N omega-nitro-L-arginine methyl ester (L-NAME) at concentrations of 1, 10, and 100 microM were 2.5 +/- 0.6, 2.9 +/- 0.7, and 4.8 +/- 0.4, respectively. N omega-monomethyl-L-arginine (L-NMMA) showed a similar effect and a biologically inactive isomer of L-NMMA, D-NMMA, showed no effect. These results demonstrate that basal levels of NO play a role in modulating microvessel permeability different from that due to NO produced in response to inflammatory agents. In the activated state NOS inhibitors attenuated the increased microvessel permeability in response to ionomycin and ATP [P. He, B. Liu, and F. E. Curry. Am. J. Physiol. 272 (Heart Circ. Physiol. 41): H176-H185, 1997]. The transient increase in basal permeability induced by NOS inhibitors was not accompanied by an increase in endothelial cell [Ca2+]i and did not require the presence of extracellular calcium. Application of ketotifen, a mast cell stabilizer, and an iron-chelating reagent, deferoxamine mesylate, attenuated the transient increase in Lp induced by L-NMMA, suggesting that basal NO may have an important antioxidant role in regulating normal permeability.
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PMID:Effect of nitric oxide synthase inhibitors on basal microvessel permeability and endothelial cell [Ca2+]i. 927 92

Tryptophan hydroxylase requires Fe2+ for in vitro enzyme activity. In this study, the intracellular activity of tryptophan hydroxylase was assessed by applying 3-hydroxybenzylhydrazine (NSD-1015), an inhibitor of aromatic l-amino acid decarboxylase, to monolayer cultures of RBL2H3 cells, a serotonin producing mast cell line. The effect of manipulating intracellular 'free' iron levels on enzyme activity was analyzed by administration of iron chelators. Desferrioxamine (DFO) suppressed the intracellular enzyme activity. Salicylaldehyde isonicotinoyl hydrazone (SIH) also suppressed enzyme activity, but stimulated it when administered in the Fe-bound form. Hemin also stimulated enzyme activity, which progressively increased over several hours to more than sixfold the initial level. DFO and SIH inhibited the hemin stimulatory effect when administered simultaneously with hemin. Both suppression and stimulation with these chelators took place without a significant decrease or increase in the amount of enzyme. These results indicate that there was an inadequate supply of Fe2+ in the cells to support full activity of tryptophan hydroxylase.
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PMID:Iron dependence of tryptophan hydroxylase activity in RBL2H3 cells and its manipulation by chelators. 1021 90

To investigate the direct effect of leukocyte adherence to microvessel walls on microvessel permeability, we developed a method to measure changes in hydraulic conductivity (L(p)) before and after leukocyte adhesion in individually perfused venular microvessels in frog mesentery. In 19 microvessels that were initially free of leukocyte sticking or rolling along the vessel wall, control L(p) was measured first with Ringer-albumin perfusate. Blood flow was then restored in each vessel with a reduced flow rate in the range of 30-116 microm/s to facilitate leukocyte adhesion. Each vessel was recannulated in 45 min. The mean number of leukocytes adhering to the vessel wall was 237 +/- 22 leukocytes/mm(2). At the same time, L(p) increased to 4.7 +/- 0.5 times the control value. Superfusion of isoproterenol (10 microM) after leukocyte adhesion brought the increased L(p) back to 1.1 +/- 0.2 times the control in 5-10 min (n = 9). Superfusing isoproterenol before leukocyte adhesion prevented the increase in L(p) (n = 6). However, the number of leukocytes adhering to the vessel wall was not significantly affected. These results demonstrated that leukocyte adhesion caused an increase in microvessel permeability that could be prevented or restored by increasing cAMP levels in endothelial cells using isoproterenol. Thus cAMP-dependent mechanisms that regulate inflammatory agent-induced increases in permeability also modulate leukocyte adhesion-induced increases in permeability but act independently of mechanisms that regulate leukocyte adhesion to the microvessel wall. Application of ketotifen, a mast cell stabilizer, and desferrioxamine mesylate, an iron-chelating reagent, attenuated the increase in L(p) induced by leukocyte adhesion, suggesting the involvement of oxidants and the activation of mast cells in leukocyte adhesion-induced permeability increase. Furthermore, with the use of an in vivo silver stain technique, the locations of the adherent leukocytes on the microvessel wall were identified quantitatively in intact microvessels.
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PMID:Leukocyte adhesion and microvessel permeability. 1077 50

Intracellular histamine (HA) and cytochrome P450 monooxygenases (P450) each have been proposed as mediators of cell function, growth, and proliferation. The P450 family of heme enzymes is found in virtually all cells and generates, transforms, or inactivates steroids and other lipids that participate in cell regulation. We previously demonstrated a second messenger role for HA in blood platelets and the formation of a HA-P450 heme complex when exogenous HA was added to microsomes isolated from rat liver cells or to purified human P450 isozymes. Employing a radioimmunoassay, we now demonstrate that rat liver slices, microsomes derived from the livers of adult male rats and mast cell-deficient mice, and hepatoma cells, all contain endogenous HA. HA release from microsomes into the incubation medium, as determined by radioimmunoassay, is enhanced in the presence of carbon monoxide, steroids, and certain drugs, all agents that unite either directly with the iron atom or bind elsewhere within the heme cavity. Rat liver slices preincubated with (3)H-HA release labeled amine into the medium in the presence of those same ligands. These findings provide evidence of an in situ HA-P450 complex and offer further support that the imidazole, HA, is a physiological, intracellular modulator of cytochromes P450 in liver cells, and perhaps of these and other heme proteins in tissues in general.
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PMID:Displacement of histamine from liver cells and cell components by ligands for cytochromes P450. 1196 21

Modified Hbs are being developed as "blood substitutes," but intravascular injection of diaspirin cross-linked Hb (DBBF-Hb) can produce venular leakage. Hb toxicity may arise from reactive oxygen species, so the antioxidant sodium selenite (Na(2)SeO(3)) was used in an attempt to reduce leak formation. In anesthetized Sprague-Dawley rats, one-half of which received 2 x 10(-6) g/ml Na(2)SeO(3) in their drinking water for 3 wk, the mesenteric microvasculature was perfused with 2 mg/ml DBBF-Hb (N = 8) for 10 min. Controls (N = 7) received saline. This was followed by perfusion with FITC-albumin for 3 min, fixation, and microscopic examination. In rats given DBBF-Hb, Na(2)SeO(3) significantly reduced leak number, leak area, and mast cell degranulation. Venular leakage was also reduced in rats that only received Na(2)SeO(3) locally during DBBF-Hb perfusion. However, Na(2)SeO(3) did not affect animals receiving cyanomet-DBBF-Hb instead of DBBF-Hb and significantly increased leak number and mast cell degranulation in animals receiving saline. In vitro, Na(2)SeO(3) reduced the oxidation rate of DBBF-Hb while in the presence of oxidants. These results suggest that Na(2)SeO(3) reduces DBBF-Hb-induced microvascular leakage partly by retarding the oxidation of its heme iron.
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PMID:Sodium selenite reduces hemoglobin-induced venular leakage in the rat mesentery. 1238 16

We investigated the expression and the role of hypoxia-inducible factor 1alpha (HIF-1alpha) on the desferrioxamine (DFX)-induced cytokine production in human mast cells, HMC-1 cells. HIF-1alpha mRNA was constitutively expressed in mast cell lines including the P815, RBL-2H3, and HMC-1. DFX (100 microM) resulted in a great increase in protein levels of HIF-1alpha in HMC-1 cells, but it did not affect HIF-1alpha mRNA expression. Iron (HIF-1 inhibitor) inhibited increase of HIF-1alpha and NF-kappaB protein levels. Pyrriolidine-dithiocarbamate (PDTC, NF-kappaB inhibitor) inhibited increase of NF-kappaB protein levels, but it slightly increased HIF-1alpha protein levels. In addition, DFX significantly increased the production of IL-6, IL-8, and TNF-alpha in HMC-1 (P<0.05). These increased cytokine levels were significantly inhibited by treatment of iron or PDTC in a dose-dependent manner (P<0.05). We demonstrated the regulatory effects of HIF-1alpha on the DFX-induced proinflammatory cytokine production in human mast cells for the first time. These data indicate that inflammatory cytokines seem to be under HIF-1alpha or NF-kappaB transcriptional regulation in the hypoxic conditions on mast cells.
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PMID:Expression of proinflammatory cytokines via HIF-1alpha and NF-kappaB activation on desferrioxamine-stimulated HMC-1 cells. 1282 Nov 13


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