Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The direct effects on the cartilage articular surface of three anti-inflammatory drugs (Diclofenac, Pirprofen and acetyl-salicylic acid) and of a polysulfated glycosaminoglycan (Arteparon), were studied using an in vitro system in which BALB-c mouse femoral heads were incubated with the drugs. After incubation and labeling of the negative charges of the articular surfaces with cationized ferritin, the femoral heads were examined by electron microscopy. In addition, the effect of the drugs on the aggressive action of collagenase on the articular surface was tested using the same in vitro system. Diclofenac, Pirprofen and the polysulfated glycosaminoglycan did not alter the structure or the charge properties of the surface. Acetyl salicylic acid produced a slight disruption of the articular surface. The drugs studied had no effect on the disruptive action of collagenase.
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PMID:Drug action on articular cartilage surface. An in vitro study using mouse femoral heads labeled with cationized ferritin. 295 42

Aspirin has recently been shown to increase endothelial resistance to oxidative damage. However, the mechanism underlying aspirin-induced cytoprotection is still unknown. Using cultured cells, the present study investigates the effect of aspirin on the expression of ferritin, a cytoprotective protein that sequesters free cytosolic iron, the main catalyst of oxygen radical formation. In bovine pulmonary artery endothelial cells, aspirin at low antithrombotic concentrations (0.03 to 0.3 mmol/L) induced the synthesis of ferritin protein in a time- and concentration-dependent fashion up to 5-fold over basal levels, whereas ferritin H (heavy chain) mRNA remained unaltered. Aspirin-induced cytoprotection from hydrogen peroxide toxicity was mimicked by exogenous iron-free apoferritin but not iron-loaded ferritin, demonstrating the antioxidant function of newly synthesized ferritin under these conditions. Ferritin induction by aspirin was specific in that other nonsteroidal anti-inflammatory drugs such as salicylic acid, indomethacin, or diclofenac failed to alter ferritin protein levels. Aspirin-induced ferritin synthesis was abrogated in the presence of the iron chelator desferrioxamine, pointing to an interaction of aspirin with iron-responsive activation of ferritin translation. Together, our results suggest induction of ferritin as a novel mechanism by which aspirin may prevent endothelial injury in cardiovascular disease, eg, during atherogenesis.
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PMID:Aspirin increases ferritin synthesis in endothelial cells: a novel antioxidant pathway. 959

The inhibition of covalent binding of the nascent C4b fragment of the human complement component to its natural target, immunoglobulin G, was studied. To this end, an immunoenzyme system was developed. In this ELISA method, the complement was activated on the sorbed IgG molecules and the resulting nascent C4b fragment acylated IgG or interacted with a competitive inhibitor added to the system. The inhibition constants for binding of the nascent C4b to its target were determined for immunoglobulins G1, G2, G3, G4, M, and A1, as well as for ferritin, yeast mannan, capsid polysaccharides of the Neisseria meningitidis A, B, and C serotypes, diphtheria anatoxin, epinephrine, and salicylic acid. On the basis of the experimental data, the immunoglobulin role at the activation stage of the complement regulation cascade, the relationship between the antigen immunogenicity and its ability to interact with C4b, and the direct effect of a number of therapeutic agents on the complement system were discussed. Lectins of various specificities were shown to inhibit the enzymic activation of C4 by the first complement component and the subsequent C4b sorption to its target, which allowed us to suggest that some oligosaccharide fragments of the C1s and C4 molecules are spatially close to the C1s active site and to the thioester bond of C4.
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PMID:[Inhibition of binding of activated compliment component C4b with its target]. 1169 92

The role of iron in the growth and metabolism of M. tuberculosis and other mycobacteria is discussed in relation to the acquisiton of iron from host sources, such as transferrin, lactoferrin and ferritin, and its subsequent assimilation and utilization by the bacteria. Key components involved in the acquisition of iron (as ferric ion) and its initial transport into the mycobacterial cell are extracellular iron binding agents (siderophores) which, in pathogenic mycobacteria, are the carboxymycobactins and, in saprophytic mycobacteria, are the exochelins. In both cases, iron may be transferred to an intra-envelope, short-term storage molecule, mycobactin. For transport across the cell membrane, a reductase is used which converts FeIII-mycobactin to the FeII form. The ferrous ion, possibly complexed with salicylic acid, is then shuttled across the membrane either for direct incorporation into various porphyrins and apoproteins or, for storage of iron within the bacterial cytoplasm, bacterioferritin. The overall process of iron acquisition and its utilization is under very genetic tight control. The importance of iron in the virulence of mycobacteria is discussed in relationship to the development of tuberculosis. The management of dietary iron can therefore be influential in aiding the outcome of this disease. The role of the old anti-TB compound, p-aminosalicylate (PAS), is discussed in its action as an inhibitor of iron assimilation, together with the prospects of being able to synthesize further selective inhibitors of iron metabolism that may be useful as future chemotherapeutic agents.
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PMID:Iron, mycobacteria and tuberculosis. 1467 Mar 52

The adhesion of monocytes to vascular endothelium increases in the presence of high levels of low density lipoprotein (LDL). LDL changes oxidative status of endothelial cells leading to an increased expression of cell adhesion molecules. Acetylsalicylic acid (ASA) has been shown to exert antioxidant effects in high and very high concentrations. This study was designed to demonstrate the influence of acetylsalicylic acid and its major metabolite, salicylic acid (SA), on the adhesion of monocytes to LDL-stimulated endothelial cells. Monocyte adhesion to endothelial cells was concentration-dependently inhibited by both salicylates upon stimulation of endothelial cells with TNF-alpha, oxidized LDL (oxLDL), and native LDL (nLDL). The inhibitory effect of ASA was more potent than that of SA, whereas the cyclooxygenase inhibitor ibuprofen had no effect. F2-isoprostane release from LDL-stimulated endothelial cells was reduced by simultaneous incubation with ASA or SA, whereas ibuprofen had no effect. LDL-induced activation of the transcription factor NF-kappaB was inhibited by ASA, and ferritin protein was increased when endothelial cells were incubated with this drug. These results show that acetylsalicylic acid and-less potently-salicylic acid inhibit monocyte adhesion to LDL-stimulated endothelial cells by antioxidative effects. For ASA, the observed inhibition of monocyte adhesion was accomplished with concentrations that can be reached after single oral doses of 500 mg of ASA.
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PMID:Acetylsalicylic acid inhibits monocyte adhesion to endothelial cells by an antioxidative mechanism. 1508 62

Siderophores (ferric ion chelators) are secreted by organisms in response to iron deficiency. The pathogenic enterobacterium Erwinia chrysanthemi produces two siderophores, achromobactin and chrysobactin (CB), which are required for systemic dissemination in host plants. Previous studies have shown that CB is produced in planta and can trigger the up-regulation of the plant ferritin gene AtFER1. To further investigate the function of CB during pathogenesis, we analyzed its effect in Arabidopsis (Arabidopsis thaliana) plants following leaf infiltration. CB activates the salicylic acid (SA)-mediated signaling pathway, while the CB ferric complex is ineffective, suggesting that the elicitor activity of this siderophore is due to its iron-binding property. We confirmed this hypothesis by testing the effect of siderophores structurally unrelated to CB, including deferrioxamine. There was no activation of SA-dependent defense in plants grown under iron deficiency before CB treatment. Transcriptional analysis of the genes encoding the root ferrous ion transporter and ferric chelate reductase, and determination of the activity of this enzyme in response to CB or deferrioxamine, showed that these compounds induce a leaf-to-root iron deficiency signal. This root response as well as ferritin gene up-regulation in the leaf were not compromised in a SA-deficient mutant line. Using the Arabidopsis-E. chrysanthemi pathosystem, we have shown that CB promotes bacterial growth in planta and can modulate plant defenses through an antagonistic mechanism between SA and jasmonic acid signaling cascades. Collectively, these data reveal a new link between two processes mediated by SA and iron in response to microbial siderophores.
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PMID:Microbial siderophores exert a subtle role in Arabidopsis during infection by manipulating the immune response and the iron status. 1944 37

Iron is an essential element for most living organisms, and pathogens are likely to compete with their hosts for the acquisition of this element. The bacterial plant pathogen Dickeya dadantii has been shown to require its siderophore-mediated iron uptake system for systemic disease progression on several host plants, including Arabidopsis thaliana. In this study, we investigated the effect of the iron status of Arabidopsis on the severity of disease caused by D. dadantii. We showed that symptom severity, bacterial fitness and the expression of bacterial pectate lyase-encoding genes were reduced in iron-deficient plants. Reduced symptoms correlated with enhanced expression of the salicylic acid defence plant marker gene PR1. However, levels of the ferritin coding transcript AtFER1, callose deposition and production of reactive oxygen species were reduced in iron-deficient infected plants, ruling out the involvement of these defences in the limitation of disease caused by D. dadantii. Disease reduction in iron-starved plants was also observed with the necrotrophic fungus Botrytis cinerea. Our data demonstrate that the plant nutritional iron status can control the outcome of an infection by acting on both the pathogen's virulence and the host's defence. In addition, iron nutrition strongly affects the disease caused by two soft rot-causing plant pathogens with a large host range. Thus, it may be of interest to take into account the plant iron status when there is a need to control disease without compromising crop quality and yield in economically important plant species.
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PMID:Iron deficiency affects plant defence responses and confers resistance to Dickeya dadantii and Botrytis cinerea. 2237 84