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 unicellular green alga Chlamydomonas reinhardtii is a valuable model for studying metal metabolism in a photosynthetic background. A search of the Chlamydomonas expressed sequence tag database led to the identification of several components that form a copper-dependent iron assimilation pathway related to the high-affinity iron uptake pathway defined originally for Saccharomyces cerevisiae. They include a multicopper ferroxidase (encoded by Fox1), an iron permease (encoded by Ftr1), a copper chaperone (encoded byAtx1), and a copper-transporting ATPase. A cDNA, Fer1, encoding ferritin for iron storage also was identified. Expression analysis demonstrated that Fox1 and Ftrl were coordinately induced by iron deficiency, as were Atx1 and Fer1, although to lesser extents. In addition, Fox1 abundance was regulated at the posttranscriptional level by copper availability. Each component exhibited sequence relationship with its yeast, mammalian, or plant counterparts to various degrees; Atx1 of C. reinhardtii is also functionally related with respect to copper chaperone and antioxidant activities. Fox1 is most highly related to the mammalian homologues hephaestin and ceruloplasmin; its occurrence and pattern of expression in Chlamydomonas indicate, for the first time, a role for copper in iron assimilation in a photosynthetic species. Nevertheless, growth of C. reinhardtii under copper- and iron-limiting conditions showed that, unlike the situation in yeast and mammals, where copper deficiency results in a secondary iron deficiency, copper-deficient Chlamydomonas cells do not exhibit symptoms of iron deficiency. We propose the existence of a copper-independent iron assimilation pathway in this organism.
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PMID:Copper-dependent iron assimilation pathway in the model photosynthetic eukaryote Chlamydomonas reinhardtii. 1245 93

Heme oxygenase-1 (HO-1) cleaves the porphyrin ring of heme into carbon monoxide, Fe2+, and biliverdin, which is then converted into bilirubin. Heme-derived Fe2+ induces the expression of the iron-sequestering protein ferritin and activates the ATPase Fe2+-secreting pump, which decrease intracellular free Fe2+ content. Based on the antioxidant effect of bilirubin and that of decreased free cellular Fe2+, we questioned whether HO-1 would modulate the expression of proinflammatory genes associated with endothelial cell (EC) activation. We tested this hypothesis specifically for the genes E-selectin (CD62), ICAM-1 (CD54), and VCAM-1 (CD106). We found that HO-1 overexpression in EC inhibited TNF-alpha-mediated E-selectin and VCAM-1, but not ICAM-1 expression, as tested at the RNA and protein level. Heme-driven HO-1 expression had similar effects to those of overexpressed HO-1. In addition, HO-1 inhibited the activation of NF-kappaB, a transcription factor required for TNF-alpha-mediated up-regulation of these genes in EC. Bilirubin and/or Fe2+ chelation mimicked the effects of HO-1, whereas biliverdin or carbon monoxide did not. In conclusion, HO-1 inhibits the expression of proinflammatory genes associated with EC activation via a mechanism that is associated with the inhibition of NF-kappaB activation. This effect of HO-1 is mediated by bilirubin and/or by a decrease of free intracellular Fe2+ but probably not by biliverdin or carbon monoxide.
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PMID:Heme oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activation. 1500 56

To identify genes associated with insulin-like growth factor-I receptor (IGF-IR)-mediated cellular transformation, we isolated genes that are differentially expressed in R- cells (derived from the IGF-IR knockout mouse) and R+ cells (R- cells that overexpress the IGF-IR). From these, 45 genes of known function were expressed at higher levels in R+ cells and 22 were expressed at higher levels in R- cells. Differential expression was confirmed by Northern blot analysis of R+ and R- cells. Genes expressed more abundantly in R+ cells are associated with (1) tumour growth and metastasis including, betaigH3, mts1, igfbp5 protease, and mystique; (2) cell division, including cyclin A1 and cdk1; (3) signal transduction, including pkcdeltabp and lmw-ptp; and (4) metabolism including ATPase H+ transporter and ferritin. In MCF-7 cells IGF-I induced expression of two genes, lasp-1 and mystique, which could contribute to metastasis. Lasp-1 expression required activity of the PI3-kinase signalling pathway. Mystique was highly expressed in metastatic but not in androgen-dependent prostate cancer cell lines and Mystique overexpression in MCF-7 cells promoted cell migration and invasion. We conclude that genes identified in this screen may mediate IGF-IR function in cancer progression.
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PMID:Gene expression profiles in cells transformed by overexpression of the IGF-I receptor. 1594 Feb 54

Hispidulin (6-methoxy-5,7,4'-trihydroxyflavone) and eupafolin (6-methoxy-5,7,3',4'-tetrahydroxyflavone), are flavonoids found in the leaves of Eupatorium litoralle. They have recognized antioxidant and antineoplastic properties, although their action mechanisms have not been previously described. We now report the effects of hispidulin on the oxidative metabolism of isolated rat liver mitochondria (Mit) and have also investigated the prooxidant and antioxidant capacity of both flavonoids. Hispidulin (0.05-0.2 mM) decreased the respiratory rate in state III and stimulated it in state IV, when glutamate or succinate was used as oxidizable substrate. Hispidulin inhibited enzymatic activities between complexes I and III of the respiratory chain. In broken Mit hispidulin (0.2 mM) slightly inhibited ATPase activity (25%). However, when intact Mit were used, the flavonoid stimulated this activity by 100%. Substrate energized mitochondrial swelling was markedly inhibited by hispidulin. Both hispidulin and eupafolin were able to promote iron release from ferritin, this effect being more accentuated with eupafolin with the suggestion of a possible involvement of H2O2 in the process. Hispidulin was incapable of donating electrons to the stable free radical DPPH, while eupafolin reacted with it in a similar way to ascorbic acid. The results indicate that hispidulin as an uncoupler of oxidative phosphorylation, is able to release iron from ferritin, but has distinct prooxidant and antioxidant properties when compared to eupafolin.
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PMID:Hispidulin: antioxidant properties and effect on mitochondrial energy metabolism. 1629 60

Virulence of Mycobacterium tuberculosis and related pathogenic mycobacteria requires the secretion of early secretory antigenic 6 kDa (ESAT-6) and culture filtrate protein 10 (CFP-10), two small proteins that lack traditional signal sequences and are exported through an alternative secretion pathway encoded primarily by the RD1 genetic locus. Mutations affecting the synthesis or secretion of ESAT-6 or CFP-10 attenuate the virulence of M. tuberculosis in murine models of infection. However, the specific functions of these proteins and of their secretion system are currently unclear. In this study, we isolated a mutant of Mycobacterium marinum defective in the secretion of ESAT-6 and CFP-10. The mutation was localized within MM5446, which is orthologous to Rv3871 of M. tuberculosis H37Rv and encodes an ATPase that is a component of the ESAT-6/CFP-10 secretion system. The mutant bacteria were unable to replicate within J774 macrophages although their growth in 7H9 medium was equivalent to the parental strain. Phagosome maturation and acidification were analysed in infected macrophages by confocal and electron microscopy using the late endosome/lysosome marker LAMP-1, along with various fluid-phase markers such as rhodamine-dextran and ferritin and the acidotropic dye LysoTracker Red. These studies demonstrated that while the wild-type parental strain of M. marinum primarily resides in a poorly acidified, non-lysosomal compartment, a significantly higher percentage of the MM5446 mutant organisms are in acidified compartments. These results suggest that the ESAT-6/CFP-10 secretion system plays a role in preventing phagolysosomal fusion, a novel function that accounts for the ability of bacteria to survive inside host cells. This finding provides a mechanism by which the ESAT-6/CFP-10 secretion system potentiates the virulence of pathogenic mycobacteria.
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PMID:The ESAT-6/CFP-10 secretion system of Mycobacterium marinum modulates phagosome maturation. 1692 61

Airway epithelial cells prevent damaging effects of extracellular iron by taking up the metal and sequestering it within intracellular ferritin. Epithelial iron transport is associated with transcellular movement of other cations including changes in the expression or activity of Na, K-ATPase and epithelial Na(+) channel (ENaC). Given this relationship between iron and Na(+), we hypothesized that iron uptake by airway epithelial cells requires concurrent Na(+) transport. In preliminary studies, we found that Na(+)-free buffer blocked iron uptake by human airway epithelial cell. Na(+) channels inhibitors, including furosemide, bumetanide, and ethylisopropyl amiloride (EIPA) significantly decreased epithelial cell concentrations of non-heme iron suggesting that Na(+)-dependent iron accumulation involves generalized Na(+) flux into the cells rather than participation of one or more specific Na(+) channels. In addition, efflux of K(+) was detected during iron uptake, as was the influx of phosphate to balance the inward movement of cations. Together, these data demonstrate that intracellular iron accumulation by airway epithelium requires concurrent Na(+)/K(+)exchange.
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PMID:Iron accumulation in bronchial epithelial cells is dependent on concurrent sodium transport. 1848 68

Perimicrovillar membranes (PMM) are structures present on the surface of midgut epithelial cells of the hematophagous insect, Rhodnius prolixus. They cover the microvilli and are especially evident 10 days after blood meal, providing the compartmentalization of the enzymatic processes in the intestinal microenvironment. Using an enzyme cytochemical approach, Mg2+-ATPase and ouabain-sensitive Na+K+-ATPase activities were observed in the plasma (or microvillar) membrane (MM) of midgut cells and in the PMM. In contrast, alkaline phosphatase was only detected in MM. Using cationized ferritin and colloidal iron hydroxide particles, anionic sites were found only on the luminal surface of the PMM. Using fluorescein isothiocyanate (FITC)-labeled lectins, residues of alpha-d-galactose, mannose, N-acetyl-neuraminic acid, N-acetyl-d-galactosamine and N-acetyl-galactosamine-alpha-1,3-galactose were detected on the apical surface of posterior midgut epithelial cells. On the other hand, using FITC-labeled neoglycoproteins (NGP) it was possible to detect the presence of carbohydrate binding molecules (CBM) recognizing N-acetyl-d-galactosamine, alpha-d-mannose, alpha-l-fucose and alpha-d-glucose in the posterior midgut epithelium. The use of digitonin showed the presence of sterols in the MM and PMM. These results have led the authors to suggest that for some components the PMM resembles the MM lining the midgut cells of R. prolixus, composing a system which covers the microvilli and stretches to the luminal space.
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PMID:Cytochemical characterization of microvillar and perimicrovillar membranes in the posterior midgut epithelium of Rhodnius prolixus. 1860 23

Human RECQL4 protein was expressed in insect cells using a baculovirus protein expression system and it was purified to near homogeneity. The protein sedimented at a position between catalase (230 kDa) and ferritin (440 kDa) in glycerol gradient centrifugation, suggesting that it forms homo-multimers. Activity to displace annealed 17-mer oligonucleotide in the presence of ATP was co-sedimented with hRECQL4 protein. In ion-exchange chromatography, both DNA helicase activity and single-stranded DNA-dependent ATPase activity were co-eluted with hRECQL4 protein. The requirements of ATP and Mg for the helicase activity were different from those for the ATPase activity. The data suggest that the helicase migrates on single-stranded DNA in a 3'-5' direction. These results suggest that the hRECQL4 protein exhibits DNA helicase activity.
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PMID:DNA helicase activity in purified human RECQL4 protein. 1945 Nov 48

HO-1 (haem oxygenase-1) is a ubiquitously expressed inducible enzyme degrading haem to CO, biliverdin and Fe(2+). Its activation reduces oxidative stress in cells and inhibits inflammation, both due to removal of haem and because of the biological activity of HO-1 products. CO may act similarly to NO, activating soluble guanylate cyclase and elevating cGMP production. It inhibits platelet aggregation, reduces leucocyte adhesion, decreases apoptosis and lowers the production of some pro-inflammatory cytokines. Biliverdin is converted into bilirubin by biliverdin reductase, and both compounds are potent antioxidants, free radical scavengers and inhibitors of the complement cascade. Iron ions can be potentially toxic, increasing the generation of hydroxyl radicals, but simultaneous induction of ferritin and activation of the Fe-ATPase iron transporter protects cells from oxidative stress. Importantly, basal and induced expression of HO-1 is very variable in the human population because of the highly polymorphic (GT)n fragment in the promoter, which may have clinical relevance. The recognized roles of HO-1 are far beyond cytoprotection. The enzyme is important in the regulation of cell proliferation, differentiation and apoptosis. Its activity improves neovascularization, attenuates inflammation and modulates the immune response, thereby influencing carcinogenesis, wound healing, transplant survival and the progression of cardiovascular diseases. Recent results indicate that HO-1 may also act through the regulation of microRNAs, which suggests a much broader involvement of HO-1 in the modulation of cell functions and offers a potential explanation for some well-known activities whose mechanism has hitherto been unclear.
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PMID:Haem oxygenase-1: non-canonical roles in physiology and pathology. 2199 9

Browning is a critical problem, which often limits the shelf life and marketability in fresh-cut lotus tuber. Proteome level changes in response to the browning metabolism were investigated using two-dimensional electrophoresis (2-DE) and MALDI-TOF-TOF. A total of 34 functional protein spots were identified by comparing 2-DE protein patterns of fresh-cut lotus tuber before and after browning. These 34 identified proteins could be classified into 7 functional groups based on the NCBI database, that is, material and energy metabolism (35%), stress response (20%), respiration metabolism (12%), cell structure (12%), signal transduction (6%), gene expression regulation (6%), and unclassified proteins (9%). The group with the greatest difference in protein expression was related to material metabolism and regulation, reactive oxygen species metabolism, and respiratory control. The distinct proteins included universal stress protein (USP), superoxide dismutase (SOD), peroxidase (POD), ferritin, and ATPase.
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PMID:Changes of protein profile in fresh-cut lotus tuber before and after browning. 2245 95


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