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Fouquet, Guillemette. "Régulation de l’érythropoïèse : rôle des récepteurs à la transferrine et d’un phytoestrogène." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS293.
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L’érythropoïèse est un processus extrêmement prolifératif, et qui doit donc être très étroitement régulé. L’érythropoïétine (EPO) est l’un des facteurs absolument nécessaires à l’érythropoïèse. Cependant, dans la moelle osseuse, la quantité d'EPO circulante est sous-optimale et la capacité des érythroblastes à survivre dépend donc de leur sensibilité à l'EPO. Les facteurs modulant la réponse à l'EPO au cours de l'érythropoïèse sont encore largement inconnus.Nous avons donc voulu explorer plusieurs facteurs pouvant potentiellement être impliqués dans la régulation de l’érythropoïèse et plus précisément dans la réponse à l’EPO : tout d’abord, la transferrine ainsi que ses récepteurs (TfR), la transferrine et le TfR1 étant également essentiels à l’érythropoïèse, ainsi qu’un phytoestrogène provenant d’une plante nommée Curcuma comosa, les oestrogènes étant eux aussi connus pour favoriser l’érythropoïèse.Concernant la transferrine, nous avons voulu principalement explorer son rôle sur la signalisation, ayant récemment montré au laboratoire que le TfR1, essentiellement connu pour son rôle dans l’endocytose du fer, est également capable d’entraîner une signalisation.Nous avons montré que la transferrine potentialise la stimulation induite par l’EPO des voies ERK, AKT et STAT5. Cet effet est conservé même en l’absence d’endocytose du TfR1. Aucune coopération n’a été trouvée entre la transferrine et le stem cell factor (SCF).Nous avons également observé qu’en l’absence du TfR2, il existe une augmentation de l’expression de l’EPO-R et de la signalisation induite par l’EPO, sans impact de la transferrine dans ce contexte. Par ailleurs, nous avons montré que le Curcuma comosa améliore la prolifération et la différenciation des progéniteurs érythroïdes précoces, par un mécanisme de potentialisation de la signalisation induite par l’EPO impliquant le récepteur aux oestrogènes ER-α.En conclusion, la transferrine et ses récepteurs, ainsi qu’un phytoestrogène et l’ER-α, sont impliqués dans la régulation de l’érythropoïèse via leur action sur la signalisation induite par l’EPO. L’approfondissement de ces données pourrait ouvrir de nouvelles pistes thérapeutiques dans le traitement de l’anémieErythropoiesis is an extremely proliferative process and must be very closely regulated. Erythropoietin (EPO) is one of the major factors necessary for erythropoiesis. However, in the bone marrow, the amount of circulating EPO is suboptimal and the ability of erythroblasts to survive therefore depends on their sensitivity to EPO. The factors modulating the response to EPO during erythropoiesis are still largely unknown. We therefore wanted to explore several factors that could potentially be involved in the regulation of erythropoiesis and more specifically in the response to EPO: first, transferrin and its receptors (TfR), transferrin and TfR1 being also essential for erythropoiesis, as well as a phytoestrogen from a plant called Curcuma comosa, as estrogens are also known to promote erythropoiesis. Regarding transferrin, we mainly wanted to explore its role on signaling, having recently shown in the laboratory that TfR1, essentially known for its role in iron endocytosis, is a signaling-competent receptor. We have shown that transferrin potentiates EPO-induced stimulation of the ERK, AKT and STAT5 pathways. This effect is maintained even in the absence of TfR1 endocytosis. No cooperation was found between transferrin and stem cell factor (SCF). We also observed that in the absence of TfR2, there is an increase in EPO-R expression and EPO-induced signaling, without any impact of transferrin in this context.In addition, we have shown that Curcuma comosa improves the proliferation and differentiation of early erythroid progenitors through a mechanism involving the ER-α estrogen receptor, able to potentiate EPO-induced signaling. In conclusion, transferrin and its receptors, as well as a phytoestrogen and ER-α, are involved in the regulation of erythropoiesis through their action on EPO-induced signaling. Further investigation of these data could provide new therapeutic strategies in the treatment of anemia
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Sharma, Nita Devi. "Molecular definition of the interaction of transferrin with the meningococcal and human transferrin receptor." Thesis, Birkbeck (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338641.
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Stokes, Russell Hayden. "Meningococcal transferrin binding proteins A and B form a functional human serum transferrin receptor." Thesis, King's College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313503.
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Booyjzsen, Claire. "Fibril formation by human transferrin." Thesis, University of Warwick, 2011. http://wrap.warwick.ac.uk/51615/.
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There is a well-established connection between anomalous protein aggregates and disease, exemplified by the amyloidoses. Many neurological disorders such as Al heimer’s and Parkinson’s disease also show increased concentrations of iron deposits along with protein fibres. The increased metal concentrations observed in these instances have yet to be fully understood or explained. The research in this thesis is concerned with the aggregation of the protein transferrin, especially on surfaces. Human serum transferrin is an ~80 kDa iron-transporting glycoprotein found at 35 μM in the blood. It is also the body’s generic metal transporter, not only of the “natural” metals iron and manganese but also of metals used to detect or treat disease such as gallium and ruthenium. It has recently been reported from this laboratory that some batches of human serum transferrin can form fibrils on surfaces. This appeared to occur preferentially at lower salt and protein concentrations. The fibres exhibited a distinctive subunit structure with a consistent width of ca. 200 nm, and dark periodic striations along the length of the fibres apparently due to deposition of ferric (oxy)hydroxo mineral, lepidocrocite. The ability of human serum transferrin and recombinant (largely deglycosylated) transferrin to form fibres on surfaces has been investigated. Batches which formed fibres appeared to have normal primary, secondary and tertiary structures, and iron-binding properties, as determined by UV-visible and circular dichroism, spectroscopy, isothermal titration calorimetry, and ion-mobility-mass spectrometry. Dye binding experiments in solution suggested that classical amyloid fibres are not formed in solution. However, investigations of gas-phase conformations of transferrin from fibre-forming solutions, by ion mobility mass spectrometry, revealed an intrinsic transferrin dimer and higher order structures. These were separated by chromatography. Dimeric and monomeric transferrin were imaged on surfaces using transmission electron microscopy and atomic force microscopy. Only the dimer yielded structured aggregates, circular subunits composed of transferrin fibres. Dynamic light scattering and polyacrylamide gel electrophoresis further confirmed the presence of higher order structures in solution. Hence dimerisation of transferrin appears to trigger the initiation formation of fibrils possibly by pre-ordering of the protein in solution. Further atomic force microscopy analysis of deposited transferrin on mica surfaces by atomic force microscopy revealed the deformation (flattening) of the protein perhaps indicating structural flexibility that may be important for fibril formation. Some long, thin fibrils with distinct curvature were detectable by AFM. This appears to support the hypothesis that many proteins can exhibit fibril-like behaviour under specific conditions. If transferrin aggregation can occur when the protein is deposited on natural surfaces in the body, these findings may have important implications for certain physiological disorders including neurological conditions and lead to new treatments.
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Baptista, Rafaela Speranza [UNESP]. "Proteinograma sérico de cordeiros nascidos a termo ou prematuros." Universidade Estadual Paulista (UNESP), 2016. http://hdl.handle.net/11449/146742.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Ao final da gestação o neonato deve estar preparado, por meio de modificações funcionais e estruturais de órgãos e sistemas para dar início à vida extra-uterina. Os animais prematuros nascem antes deste processo estar completo, apresentando falhas na maturação. O objetivo deste estudo foi tentar identificar por meio da técnica de eletroforese em gel de poliacrilamida em dodecil sulfato de sódio (SDS-PAGE) proteínas de fase aguda, dentre elas, albumina, ceruloplasmina, transferrina, haptoglobina, glicoproteína ácida e imunoglobulinas A e G, que possam indicar a maturação no neonato prematuro. Os cordeiros foram divididos em seis grupos experimentais (parto normal, cesárea a termo, cesárea prematura, cesárea prematura com administração pré-parto materna de dexametasona, cesárea com administração de surfactante nos prematuros e cesárea prematura com administração pré-parto materna de dexametasona e surfactante ao neonato). Os resultados indicaram que após a administração de colostro, independente do tratamento, os valores séricos de proteína total e imunoglobulinas G aumentaram, indicando que há transferência de imunidade passiva através do trato gastrointestinal. A transferrina tem seus teores superiores em animais com idade gestacional superior, demonstrando potencial para ser utilizado como marcador de maturação neonatal.
At the end of gestation the neonate should be prepared, with functional and structural modifications of organs and systems to initiate extrauterine life. Premature animals are born before this process is complete, presenting maturation failures. The aim of this study was to identify an acute phase protein, such as albumin, ceruloplasmin, transferrin, haptoglobin, acid glycoprotein and immunoglobulins A and G, that demonstrates that different treatments indicate a maturation in the premature neonate using sodium dodecyl sulfate polyacrylamide gel electrophoresis technique (SDS-PAGE). The lambs were divided into six experimental groups (normal birth, full-term cesarean section at normal time of gestation, premature cesarean section, premature cesarean section whose mothers received prepartum dexamethasone, cesarean section giving surfactante to the prematures and premature cesarean giving prepartum dexamethasone to the mothers and surfactant to the neonate). The results indicated that after administration of colostrum, regardless of treatment, total serum protein and immunoglobulins increased, showing the transfer of passive immunity through the gastrointestinal tract. Transferrin has higher levels in animals with higher gestational age, demonstrating potential as a marker of neonatal maturation.
FAPESP: 2011/18810-3
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Baptista, Rafaela Speranza. "Proteinograma sérico de cordeiros nascidos a termo ou prematuros /." Araçatuba, 2016. http://hdl.handle.net/11449/146742.
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Orientador: Luiz Claudio Nogueira MendesCoorientadora: Fernanda Bovino
Banca:Francisco Leydson Formiga Feitosa
Banca:Marcio Carvalho da Costa
Resumo: Ao final da gestação o neonato deve estar preparado, por meio de modificações funcionais e estruturais de órgãos e sistemas para dar início à vida extra-uterina. Os animais prematuros nascem antes deste processo estar completo, apresentando falhas na maturação. O objetivo deste estudo foi tentar identificar por meio da técnica de eletroforese em gel de poliacrilamida em dodecil sulfato de sódio (SDS-PAGE) proteínas de fase aguda, dentre elas, albumina, ceruloplasmina, transferrina, haptoglobina, glicoproteína ácida e imunoglobulinas A e G, que possam indicar a maturação no neonato prematuro. Os cordeiros foram divididos em seis grupos experimentais (parto normal, cesárea a termo, cesárea prematura, cesárea prematura com administração pré-parto materna de dexametasona, cesárea com administração de surfactante nos prematuros e cesárea prematura com administração pré-parto materna de dexametasona e surfactante ao neonato). Os resultados indicaram que após a administração de colostro, independente do tratamento, os valores séricos de proteína total e imunoglobulinas G aumentaram, indicando que há transferência de imunidade passiva através do trato gastrointestinal. A transferrina tem seus teores superiores em animais com idade gestacional superior, demonstrando potencial para ser utilizado como marcador de maturação neonatal.
Abstract:At the end of gestation the neonate should be prepared, with functional and structural modifications of organs and systems to initiate extrauterine life. Premature animals are born before this process is complete, presenting maturation failures. The aim of this study was to identify an acute phase protein, such as a lbumin, ceruloplasmin, transferrin, haptoglobin, acid glycoprotein and immunoglobulins A and G, that demonstrates that different treatments indicate a maturation in the premature neonate using sodium dodecyl sulfate polyacrylamide gel electrophoresis technique (SDS - PAGE) . The lambs were divided into six experimental groups (normal birth, full - term cesarean section at norma l time of gestation, premature cesarean section, premature cesarean section whose mothers received prepartum dexamethasone, cesarean section giving surfactante to the prematures and premature cesarean giving prepartum dexamethasone to the mothers and surfactant to the n eonate). The results indicated that after administration of colostrum, regardless of treatment, total serum protein and immunoglobulins increased, showing the transfer of passive immunity through the gastrointestinal tract. Transfer rin has higher levels in animals with higher gestational age, demonstrating potential as a marker of neonatal maturation
Mestre
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Trimble, Esther R. "Carbohydrate-deficient transferrin and alcohol abuse." Thesis, Queen's University Belfast, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388195.
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Kaur, Ishwinder. "Nuclear translocation and transferrin-transferrin receptor interaction of IPSE/[alpha}-1, a secretory glycoprotein from Schistosoma mansoni." Thesis, University of Nottingham, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.508222.
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Helminthic parasites have evolved with immune modulating machinery to manipulate their host's immune response and thus survive unscathed for years and in some cases even decades. However, the underlying molecular mechanisms governing the host-parasite relationship are still largely unknown. Therefore detailed investigation and evaluation of parasitic molecules is desirable. One such molecule worthy of attention is IPSE/a-1 (lnterleukin-4 inducing principle from schistosome eggs). IPSE/a-1 is a secretory glycoprotein produced exclusively by the egg stage of Schistosoma mansoni, which activates human basophils in non-antigen specific IgE dependent mechanisn;t. Sequence analyses of IPSE/a-1 using bioinformatic subcellular localisation prediction tools revealed a putative nuclear localisation signal (NLS) at the C-terminus. The present work was conducted to confirm whether this sequence ('125-PKRRRTY-131') was both necessary and sufficient for nuclear localisation of IPSE/a-1 and other heterologous GFP proteins. A plasmid encoding EGFP-IPSE/a-1, as well as a truncated mutant lacking amino acids 125-134, was transfected into Huh7 and U2-0S cell lines, and fluorescence of the fusion protein was determined by confocal laser scanning microscopy. EGFP-IPSE/a-1 was found to be exclusively nuclear, whereas the mutant displayed both nuclear and cytoplasmic staining. Furthermore, insertion of the IPSE/a-1 NLS into a tetra-EGFP construct showed nuclear localisation, and alanine scanning mutagenesis revealed a requirement for the KRRR residues. IPSE/a-l also binds to transferrin, which lead to downstream effect on cellular proliferation. Besides, fluorescence microscopy revealed that recombinant IPSE/a-l protein added exogenously to culture medium was internalized by variant Chinese hamster ovary (CRO) cells expressing the human transferrin receptor and was found in the nuclei of these cells Western blotting further confirmed this temporal relocalisation of IPSE/a-l from cytosolic to nuclear fractions. In addition, IPSE/a-l exhibited a DNA-binding activity that appeared to be dependent on the C-terminal NLS sequence. In summary, the main achievement of this work is the identification and characterization of a NLS in IPSE/a-l that is functional in mammalian cells, which will form the basis for further investigations into the biological significance of this nuclear targeting and DNA interaction e.g. IPSE/a-l may function as transcription factor in the nucleus. The properties of IPSE/a-l described here also make it an interesting potential vehicle for intracellular and nuclear drug delivery.
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Bergström, Jonas P. "Human serum transferrin glycosylation pattern : population differencies, analytical methodology and application as biomarker for testing of alcohol abuse and CDG /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-432-7/.
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Houldershaw, David. "The electrostatics of iron binding to transferrin." Thesis, Birkbeck (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244463.
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Bunyan, Kerry Emma. "Chemical and biological studies of manganese transferrin." Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/15569.
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This thesis is concerned with the loading of transferrin with manganese and some of its chemical and biological properties. Manganese is bound to transferrin as Mn(III) with a characteristic ligand (Tyr) to metal (Mn(III) charge-transfer band at a wavelength of 430 nm. Caeruloplasmin is shown to enhance the uptake of manganese from MnC12 by apo-hTf. However binding is often incomplete and slow. A novel method of loading hTf with Mn using KMnO4 is reported. This method leads to rapid uptake and inductively coupled plasma atomic emission spectroscopy (ICP-AES) determinants confirmed the binding of at least two Mn per hTf molecule. The possible oxidising effects of MnO4- on protein amino acid side chains was considered. In model systems MnO4- oxidises methionine to methionine sulfoxide and methionine sulfone. Evidence of structural changes in apo-hTf induced by Mn(III) binding was obtained by studies using [e-13C]Met-hTf. Preliminary work suggests that Mn(III), like several other metals studied, preferentially binds to the C-lobe first, although this may result in an open domain conformation. Fe(III) as Fe(NTA)2 was found to displace Mn(III) from hhTf but displacement was slower when hTf had been loaded using KMnO4 rather than MnCl2. KMnO4 was not able to displace Fe(III) from Fe2-hTf. Attempts to crystallise Mn-hTf to characterise these structural changes proved difficult. Crystals grew but were of poor quality and did not diffract. Many large crystals were obtained from solutions of Fe2-hTf. The crystals were red/orange and ellipsoidal in shape. Of the Fe2-hTf crystals grown, one diffracted to 3.3 Å with the data being complete to 90%, but not enough information was gained for adequate molecular replacement and structural solution.
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Price, Gregory A. "Immunogenicity of the Gonococcal Transferrin Binding Proteins." VCU Scholars Compass, 2005. http://scholarscompass.vcu.edu/etd_retro/76.
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The gonococcal transferrin binding proteins (Tbps) are two surface-exposed outer membrane proteins, TbpA and TbpB, which together function to remove and internalized iron from human transferrin. Iron is an essential nutrient to the gonococcus, without which it cannot survive. The Tbps have been established as virulence factors, demonstrating their importance in establishing infection. Both TbpA and TbpB are well conserved among gonococcal isolates, and have been considered potential vaccine targets. Vaccine studies with the closely related species Neisseria meningitidis, have demonstrated these proteins to be protective in murine challenge studies. Though the meningococcal Tbps have demonstrated promise, no similar gonococcal vaccine experiments have been conducted prior to the current studies. Here we demonstrate purification of recombinant TbpA and TbpB. These recombinant proteins were utilized to evaluate the human immune response to these proteins during natural infections, and their immunogenicity in murine vaccine studies. Our results demonstrate a paucity of antibodies elicited to these proteins during natural infections in serum and mucosal secretions from infected individuals. From this study we hypothesized the induction of both serum and genital antibodies to these proteins could serve to protect an individual from infection. To begin testing this hypothesis, we immunized mice both intranasally (IN) and subcutaneously (s.c.) with full-length Tbps in conjunction with the B subunit of cholera toxin (Ctb) as an adjuvant. We also performed another vaccine study using domains from both proteins in genetic fusions with Ctb and E. coli heat labile toxin IIb (LtbIIb). Both studies demonstrated that these antigens were immunogenic, as Tbp-specific antibodies were elicited in the serum and vaginal washes of female Balb/C mice. Intranasal immunization however was the only route with which we were able to elicit vaginal Tbp-specific IgA, and IgG, whereas subcutaneous immunization only elicited vaginal IgG. Furthermore, we found the full-length Tbps and the Ctb/LtbIIb chimeras were able to elicit bactericidal antibodies, which were also effective in killing heterologous gonococcal strains. This body of work comprises the first published study using the gonococcal transferrin binding proteins as vaccine antigens, and highlights their potential as vaccine antigens in the development of an efficacious gonococcal vaccine.
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Hodgkins, Paul S. "Reduced metal transferrin binding in neurological diseases." Thesis, Aston University, 1992. http://publications.aston.ac.uk/12605/.
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By employing G75 gel-filtration chromotography, it has been demonstrated that human plasma gallium speciation (and by implication, Al speciation) is bimodal. Normally, gallium was predominantly bound to a high molecular weight fraction which was presumably transferrin. Literature reviews and experimental work throughout this thesis provided evidence to support this idea. An aluminium-transferrin species was assumed to be relatively non-toxic and a protective function for this complex has been suggested. A second, low molecular weight species of gallium was observed and its identity has been suggested to be citrate. The results of this thesis support the concept citrate was a gallium binding ligand present in the plasma, but there was another species (tentatively identified as phosphate) which bound gallium to a much greater degree than did citrate in the majority of samples studied. The consequence of a low molecular weight species of aluminium is the possibility that this leads to a more rapid, uncontrolled deposition of the metal in the brain compared to a transferrin mediated mechanism. Plasma speciation studies in Alzheimer's disease, Parkinson's disease, Down's syndrome, and neonates has revealed an altered ratio of the two gallium species found in control subjects. In all groups there was an increase in the potentially more neurotoxic low molecular weight species. These observations have led to a suggested mechanism of accumulation of metals in the brain, which is known to occur in the first three groups. Possible pathogenic mechanisms are described. The results can also offer an explanation to the reported increased sensitivity to the toxic effects of aluminium in the neonate. Speciation studies on normal plasma has shown the balance between high and low molecular weight species of gallium to be influenced by many physiological factors. There appears to be a fine equilibrium between both species which can be altered without any great difficulty. Therefore, in the diseased groups studied, it is possible that there are subtle biochemical changes within the circulatory system to affect the equilibrium which results in an increased low molecular weight species of aluminium. Furthermore, it has been demonstrated that there is a group of normal controls with no clinical signs of Alzheimer's or Parkinson's disease which have reduced transferrin binding. This indicates there is a population of healthy people who are at risk to the development of either disease.
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Ulin, Desirée. "Metodverifiering av ny upparbetningsmetod för kolhydratfattigt transferrin." Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-85498.
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Transferrin är ett protein som har uppgiften att transportera järn i kroppen. Transferrin är ett glykoprotein med två kolhydratkedjor med två, tre förgreningar med terminala sialinsyror. Antalet sialinsyror ger proteinet olika isoformer och benämns därefter, så som tetrasialotransferrin som har fyra terminala sialinsyror och är den vanligaste förekommande isoformen. Disialotransferrin används som en biokemisk markör för att identifiera individer som har en hög alkoholkonsumtion under en längre period. Disialotransferrin ökar i koncentrationen vid hög alkoholkonsumtion under minst 14 dagar. Den benämns som kolhydratfattigt transferrin (eng. Carbohydrate-Deficient Transferrin, CDT) och analyseras med jonbyteskromatografi. Referensvärdet för CDT är > 2,0 % då en individ har ett alkoholmissburk. Syftet med studien var att undersöka om svarstiden går att förkorta genom att optimera upparbetningen av prover och sedan utföra en metodverifiering. Optimeringen av upparbetningen omfattade en kortare inkuberingstid från nästan ett dygn till 60 minuter, förenklad tillsättning av fällningsreagens och förändrad centrifugering av proverna. I ett inledande försök analyserades 25 serumprover med olika varianter av optimerad upparbetning och resultatet jämfördes mot standardmetoden. Metodverifieringen bestod av analys av 35 serumprover med den nya upparbetningsmetoden vilket jämfördes mot standardmetoden. I analysen jämfördes även precisionen för låg (1,4 % CDT) och hög (3,2 % CDT) kontroll samt två patientprover med ett låg och hög halt av disialotransferrin med den nya metoden. Precisionen för den låga kontrollen och patientprov 1 (CV=18,05 %) visade sig var sämre än för den höga kontrollen och det patientprov 2 (CV=5,79 %). Analys av de 35 proverna visade att det var en bra överensstämmelse mellan metoderna; korrelationskoefficienten var 0,997 och ett parat t-test kunde inte detektera någon statistik signifikant skillnad mellan proverna (95 % konfidensnivå). På grund av den sämre precisionen för låga koncentrationer av disialotransferrin behöver dock den nya upparbetningsmetoden utvärderas ytterligare. Däremot är det bestämningen av CDT-halten runt 2 % som är viktig och den nya metoden har inte sämre variationskoefficient (CV %) än standardmetoden.
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Lok, Chun-nam, and 陸振南. "Regulation of transferrin receptor expression in human leukemic HL-60 cells: gene expression and cellular signaling." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1996. http://hub.hku.hk/bib/B31235141.
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Lok, Chun-nam. "Regulation of transferrin receptor expression in human leukemic HL-60 cells : gene expression and cellular signaling /." Hong Kong : University of Hong Kong, 1996. http://sunzi.lib.hku.hk/hkuto/record.jsp?B17310659.
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Giannetti, Anthony Michael Rees Douglas C. "Biochemical, biophysical, and cellular investigations of the interactions of transferrin receptor with transferrin and the hereditary hemochromatosis protein, HFE /." Diss., Pasadena, Calif. : California Institute of Technology, 2004. http://resolver.caltech.edu/CaltechETD:etd-05262004-173612.
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CABRAL, FILHO Paulo Euzébio. "Desenvolvimento de sondas multimodais baseadas em pontos quânticos para aplicações biomédicas." Universidade Federal de Pernambuco, 2016. https://repositorio.ufpe.br/handle/123456789/18443.
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Os pontos quânticos ou quantum dots (QDs) são nanocristais fluorescentes de semicondutores com propriedades ópticas únicas, tendo como principais vantagens: (1) alta resistência à fotodegradação, possibilitando o acompanhamento de eventos biológicos em tempo real e, (2) superfície ativa, permitindo a conjugação a biomoléculas que vão propiciar especificidade às marcações, além de possibilitar também sua ligação a outras nanopartículas. Com isso, é possível quantificar uma variedade de biomoléculas em células e tecidos e desenvolver nanossondas bimodais (magnético-fluorescentes) baseadas em QDs. O desenvolvimento de nanopartículas bimodais pode aliar as vantagens das técnicas baseadas em fluorescência com as de imagem por ressonância magnética (IRM). Entretanto, a obtenção de sondas bimodais é ainda um desafio, pois durante a conjugação devem ser mantidas as propriedades fluorescentes e magnéticas das nanopartículas, e com isso ainda há poucos trabalhos que façam aplicações em sistemas biológicos. O objetivo desta tese se caracteriza pelo desenvolvimento de sondas com propriedades multimodais baseadas em QDs de Telureto de Cádmio (CdTe) associadas a nanopartículas magnéticas de óxido de ferro como marcadores sítio-específicos em células cancerígenas. Inicialmente os QDs foram conjugados covalentemente à transferrina (Tf) [QDs-Tf] para a quantificação específica de seus receptores (TfRs) em células HeLa e em duas linhagens de glioblastoma (U87 e DBTRG). Através de ensaios de saturação do TfR, foi possível inferir sobre a taxa de renovação deste receptor nessas células. Os resultados mostraram que as células HeLa e as DBTRG possuem uma maior quantidade do TfR quando comparadas às U87. As DBTRG apresentaram maior taxa de renovação do TfR, quando comparadas aos outros dois tipos, demonstrando que os conjugados QDs-Tf são potenciais ferramentas para o estudo da biologia celular do câncer. Posteriormente, nanossondas bimodais (QDsMNPs), baseadas em QDs associados a nanopartículas magnéticas de óxido de ferro, foram obtidas por conjugação covalente. De acordo com as caracterizações, QDs-MNPs mantiveram suas propriedades ópticas e magnéticas e apresentaram-se como potenciais sondas inespecíficas para fluorescência e para aquisição de imagens por RM ponderadas em T2 (tempo de relaxação nuclear transversal). A conjugação prévia dos QDs a Tf, além de fornecer informações sobre a biologia do câncer, auxiliou também na padronização da marcação específica do TfR em células cancerígenas e no estabelecimento de protocolos de conjugação das sondas bimodais a Tf. Por fim, as QDs-MNPs foram conjugadas covalentemente a Tf e essa nova sonda multimodal [(QDs-MNPs)-Tf] reconheceu especificamente os TfR em células HeLa. As caracterizações indicaram que o sistema multimodal não apresentou alteração significativa nas propriedades ópticas e exibiu uma maior relaxividade transversal (r2), se mostrando igualmente potencial sonda para análise por fluorescência e IRM ponderada em T2. Neste trabalho foram obtidas nanossondas promissoras para serem aplicadas na compreensão da biologia celular do câncer, além de auxiliar em métodos diagnósticos e terapêuticos para essa doença.
Quantum dots (QDs) are fluorescent semiconductor nanocrystals with unique optical properties, which have as major advantages: (1) the high resistance to photobleaching, making possible to monitor biological events in real-time and, (2) active surface, allowing the conjugation not only with biomolecules for specific labeling, but also to other nanoparticles. Thus, it would be possible to quantify a variety of biomolecules in cells and tissues, as well as to develop bimodal nanoprobes (fluorescent-magnetic) [BNPs] based on QDs. The development of BNPs can help to combine the advantages of the fluorescence with the resonance magnetic imaging techniques. However, the preparation of bimodal probes can still be considered a challenge, since the fluorescent and magnetic nanoparticles’ properties need to be preserved after conjugation. Therefore, there are still few works applying BNPs in biological studies. The aim of this thesis was to develop nanoprobes, with multimodal properties, based on cadmium telluride (CdTe) QDs conjugated with iron oxide magnetic nanoparticles (MNPs), for site-specific labeling in cancer cells. For this, initially, QDs were covalently coupling to transferrin (Tf) [QDs-Tf] and used to quantify the transferrin receptor (TfRs) in HeLa cells as well as in two glioblastoma lines (U87 and DBTRG). Furthermore, by a TfR saturation assay, it was possible to study the recycling rate of this receptor in cells studied. The results showed that HeLa and DBTRG cells present a higher amount of TfRs when compared to U87. DBTGR showed a higher TfR recycling rate, when compared to the other two lineages, demonstrating that QDs-Tf conjugates are potential tools to study the cancer cell biology. BNPs, based on the conjugation of QDs with MNPs (QDs-MNPs), were obtained by covalent coupling. According to characterizations, the BNPs remained with their optical and magnetic properties preserved and showed to be potential unspecific probes for fluorescence analysis and for T2-weighted magnetic resonance imaging (MRI) acquisition. The conjugation of QDs to Tf, performed previously, was a valuable step not only to provide us information about the biology of cancer cells, but also for the standardization of TfR specific labeling and the establishment of protocol to conjugate the BNPs with Tf. Therefore, QDs-MNPs were also covalently coupling to Tf and this new multimodal nanotool [(QDs-MNPs)Tf] was also able to recognize specifically TfRs in HeLa cells. The multimodal nanosystems presented their fluorescent properties practically unchanged and also exhibited a higher transversal relaxivity (r2), when compared to bare BNPs, showing likewise potential to be used for fluorescence and T2-weighted MRI analyses. In this work, it was developed promising nanoprobes, able to be applied for the cancer cell biology comprehension, and with potential for helping in the improvement of diagnostic and therapeutic methods for this disease.
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Adam, Mohammed A. "Fate of the transferrin receptor during in vitro maturation of sheep reticulocytes and post-translational modifications of the transferrin receptor." Thesis, McGill University, 1986. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=70354.
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The transferrin receptor is a membrane protein which is involved in the binding and endocytosis of transferrin, the main Fe$ sp{3+}$ carrying protein. The receptor and transferrin function to provide cells with iron, an essential nutrient. As red cells mature and lose their ability to make hemoglobin, they also lose their capacity to bind transferrin and take up iron. The transferrin receptor in sheep reticulocytes has been shown to undergo externalization in vesicular form during maturation of sheep reticulocytes in vitro. Microscopic studies show that the receptor is internalized into endosomes and externalization, in vesicular form, occurs via formation of multivesicular elements (or bodies), which ultimately fuse with plasma membranes releasing the inclusion vesicles bearing the transferrin receptor. The released receptor seems intact, having the same molecular weight and $ sp{125}$I-iodo-tyrosyl tryptic peptide map as the native receptor. The externalized receptor can also bind transferrin and the anti-receptor antibody.The transferrin receptor can be fatty acylated and phosphorylated in intact cells and in isolated plasma membranes. The phosphorylation of the receptor is not affected by the binding of transferrin or anti-transferrin receptor antibody. However, $ beta$-phorbol esters can stimulate the phosphorylation of the receptor suggesting that protein kinase C may be responsible for receptor phosphorylation. During reticulocyte maturation, the externalized transferrin receptor is not phosphorylated. Furthermore, the ability of this externalized receptor to undergo phosphorylation by protein kinase C is also lost, suggesting a maturation induced change in the receptor compared to the cell associated receptor. This change may be a signal which determines whether the transferrin receptor is to be segregated for externalization during red cell maturation or recycled for iron delivery.
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Sun, Xuesong. "Iron metabolism mediated by MtsA, transferrin and desferrioxamine." View the Table of Contents & Abstract, 2006. http://sunzi.lib.hku.hk/hkuto/record/B37552995.
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Zuccola, Harmon Jay. "The crystal structure of monoferric human serum transferrin." Diss., Georgia Institute of Technology, 1992. http://hdl.handle.net/1853/26304.
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Sun, Xuesong, and 孫雪松. "Iron metabolism mediated by MtsA, transferrin and desferrioxamine." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B38722446.
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Boulton, Ian Charles. "In vitro characterisation of the meningococcal transferrin receptor." Thesis, Birkbeck (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266085.
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Oakhill, Jonathan Stuart. "Structural studies of meningococcal transferrin-binding protein A." Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271430.
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Okyere-Boakye, Ivan W. "Studies on genetic variants of human plasma transferrin." Thesis, Queen Mary, University of London, 1997. http://qmro.qmul.ac.uk/xmlui/handle/123456789/1639.
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The work presented in this thesis is concerned with the characterisation of human plasma transferrins showing abnormal electrophoretic mobilities on polyacrylamide gels. The work is divided into three studies: (i) a study of transferrin variants detected by nondenaturing polyacrylamide gel electrophoresis; (ii) a study of the plasma concentrations of individuals showing transferrin phenotypes associated with the three most common Tf C alleles, Tf Cl, Tf C2 and Tf C3; and (iii) a study of a reported nondegenerate nucleotide difference in the sequence of the cloned human transferrin gene. In the first study, six transferrin variants (3 Tf Br,,.,,, s and 3 Tf D. 5) showing abnormal electrophoretic mobilities on nondenaturing polyacrylamide gels, and the two Tf C variants, Tf Cl and Tf C2 which occur at polymorphic levels (> 1%) in human populations, were isolated and purified from human plasma. Transferrins were purified by a combination of DEAE Sephacel anion-exchange chromatography, SP. Sephadex cation-exchange chromatography and G-200 gel-filtration chromatography. A series of comparative studies were then carried out on the isolated transferrins to determine whether the six transferrin variants detected in this thesis and the Tf C2 variant, showed similar characteristics to the wild-type Tf Cl. Transferrins were studied for sialic acid content of the two glycan chains, and for molecular weights and isoelectric points of the iron-free (apo) and iron-saturated (holo) transferrin forms. Metal-binding properties were examined by studying the binding of Fe", Cu", Al" and Ga"'. Iron-binding was studied at physiological and endosomal pH (7.5 and 5.5 respectively) using FENTA as the iron donor. Binding of Cue*, Al"' and Ga'* were examined at physiological pH using CUNTA, ALNTA and GANTA respectively. The ability of transferrins to retain bound iron was examined by studying pH-induced iron release over a pH range of 6.0-4.0. Conformational stabilities were determined by studying the iron-binding abilities of apotransferrins following exposure to urea or thermal denaturation, and by studying iron loss from holo transferrins following exposure to urea or thermal denaturation. Other than expected differences in isoelectric points, and slightly faster rates of iron loss from variant holo transferrins titrated at physiological pH, all variant transferrins were found to show similar characteristics to Tf Cl, with identical molecular weights and sialic acid content, similar metal-binding properties, and similar stabilities to urea or thermal denaturation. The results indicate that the structure and function of the variant transferrins are not adversely affected by their differences in primary structure. The second study examined the relationship between plasma transferrin concentration and transferrin phenotypes representing five of the six most common Tf C phenotypes (i. e. Tf Cl, Tf C2, Tf C2-1, Tf C3-1 and Tf C3-2), to determine whether plasma concentrations were dependent on transferrin phenotype as suggested in literature. Transferrin phenotypes of 931 unrelated individuals were determined by electrophoresis of plasma on polyacrylamide isoelectric focusing gels. Plasma transferrin concentrations were determined by single radial immunodiffusion using rabbit anti-human transferrin IgG. A significant difference was found between the plasma concentrations of the five transferrin phenotypes (p < 0.01) indicating that transferrin concentration was dependent on phenotype. The results suggest that the two Tf C alleles, Tf C2 and Tf C3 are associated with low plasma concentrations. The third study was initiated to investigate a report in literature that a nondegenerate nucleotide difference of adenine for guanine at base 1086 in exon 8 of the human transferrin gene, may indicate the presence of a hitherto unrecognised transferrin variant with Asn rather than a wild-type Asp at position 310 of the amino acid sequence. The nucleotide sequenceo f exon 8 from 220 unrelatedi ndividuals showing transferrin phenotypes associated with the three most common Tf C alleles, Tf Cl, Tf C2 and Tf C3, and from 5 individuals showing abnormal transferrin phenotypes in the first study, were amplified by polymerase chain reaction. Amplified products were digested with the restriction endonuclease, Fok I which has a single recognition site in exon 8 containing the proposed wild-type guanine at base 1086, or with Bsm I which also shows a single recognition site containing the proposed adenine nucleotide. The study failed to detect the presence of the proposed transferrin variant, confirming that the wild-type guanine was present in all 225 individuals.
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Kim, Jonghan. "Pharmacokinetics and pharmacodynamics of protein turnover and production in vivo." Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1100554543.
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Thesis (Ph. D.)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains xxi, 203 p.; also includes graphics. Includes bibliographical references (p. 191-203).
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Vieillevoye, Maud. "Role and expression of transferrin receptor 2 in erythropoiesis." Thesis, Paris 5, 2013. http://www.theses.fr/2013PA05S020.
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L’érythropoïèse est le processus de différentiation d’un progéniteur érythroïde multipotent en globules rouges. La différentiation érythroïde est essentiellement contrôlée par le récepteur à l’érythropoïétine (EPOR). Nous avons montré que le récepteur à la transferrine de type 2 (TFR2) est un membre important du complexe formé par l’EPOR. Le TFR2 présente, comme l’EPOR une expression restreinte qui dépend du type cellulaire. Ainsi son expression n’a pu être détectée que dans le foie, l’érythron et l’intestin grêle. Le rôle du TFR2 a été exploré dans les hépatocytes et il a été montré qu’il joue le rôle d’un senseur de fer dans cette lignée et de ce fait contribue à l’homéostasie du fer. Nous avons déterminé le rôle du TFR2 dans les érythroblastes et montré que TFR2 est une protéine escorte de l’EPOR qui contribue à l’érythropoïèse in vitro et in vivo. De plus, nos travaux montrent que le TFR2 est requis pour la production de GDF15 (Growth Differentiation Factor 15) dans les érythroblastes. D’autre part nous avons démontré que la production de GDF15 est augmentée par l’EPO, la déplétion intracellulaire en fer et l’activité transactivatrice de P53. L’inhibition de l’expression de P53, réalisée au cours de l’étude de son rôle dans la production de GDF15, a révélé son implication dans l’érythropoïèse normale. Nous avons mis en évidence l’existence de plusieurs formes du TFR2. Deux d’entre elles résultent de l’utilisation de sites distincts d’initiation de la traduction. Ces deux isoformes sont régulée différemment au cours de la maturation des érythroblastes. La troisième isoforme, appelée TFR2 soluble (sTFR2), est relargée dans le plasma suite au clivage du TFR2. Nous avons montré que la production du sTFR2 est inhibée en présence du ligand de TFR2, la transferrine saturée en fer (holoTF) alors que le TFR2 est stabilisé dans ces mêmes conditions. Les rôles spécifiques des trois formes du TFR2 doivent encore être élucidésErythropoiesis is the differentiation process of a multipotent erythroid progenitor into red blood cells. Erythroid differentiation is primarily controlled by the erythropoietin receptor (EPOR). We showed that the Transferrin receptor 2 (TFR2) is an important member of the EPOR complex. TFR2 has like EPOR a lineage-restricted expression and can solely be detected in the liver, erythron and small intestine. TFR2 function has been explored in hepatocytes where it plays the role of an iron sensor and contributes to iron homeostasis. We determined the role of TFR2 in erythroblasts and showed that TFR2 is an escort protein for EPOR that contributes to optimal erythropoiesis in vitro and in vivo. Moreover we evidenced that TFR2 is absolutely required for the production of Growth differentiation factor 15 (GDF15) in erythroblasts. We further demonstrated that GDF15 production is increased by EPO levels, by intracellular iron depletion as well as by P53 trans-activation activity. The inhibition of P53 expression, realized for the study of its role in GDF15 production, revealed its implication in normal erythropoiesis. We evidenced that TFR2 is expressed under several forms, two of which result from the utilization of distinct translational initiation sites. These two isoforms are differently regulated during erythroid maturation. The third form called soluble TFR2 (sTFR2) is released in the plasma after TFR2 cleavage. We showed that sTFR2 production is inhibited in the presence of TFR2 ligand, iron loaded transferrin (holoTF) whereas cell surface TFR2 expression is stabilized by holoTF. The specific roles of the three forms of TFR2 expressed by erythroblasts remain to be elucidated
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Pulido-Cejudo, Gabriel. "Chemical and biological properties of iron-pyruvate-transferrin complexes." Thesis, McGill University, 1990. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74529.
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The preparation of a novel complex, ferric bromopyruvate, is described. In solutions from which most of the carbonate has been removed, ferric bromopyruvate can be used both as an iron and pyruvate source for the full iron saturation of apotransferrin. Using ferric bromopyruvate as an iron donor, iron incorporation into human apotransferrin is biphasic; the N-terminal domain is saturated three times faster than its homologous C-terminal iron binding site. Following the reaction of apotransferrin with ferric bromopyruvate, 4 moles of pyruvate per mole of transferrin are covalently bound. Based on the effect of acetylation on pyruvate and iron binding, it is suggested that lysyl residues could be the target of pyruvate bonding. However, the reaction of pyruvate with other positively charged amino acid residues cannot be excluded. The possible sites of pyruvate binding within the N-terminal domain of human serum transferrin are discussed. Covalent attachment of pyruvate to cationic amino acid residues decreased both in vitro and in vivo iron release, preferentially from the N-terminal domain of transferrin. The decreased rate of iron incorporation from iron-pyruvate-transferrin complexes by rabbit reticulocytes caused a lower iron incorporation into heme. It is suggested that an impairment of iron release from transferrin may decrease the rate of heme synthesis in reticulocytes. In vitro studies on the iron removal from iron-pyruvate-transferrin complexes showed that pyrophosphate can remove iron from this complex at an acid pH to a similar extent to the cellular mediated iron release from this complex. Based on this data, a model for the intravesicular iron release from transferrin is proposed.
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Yoon, Hye-Sun Melissa 1977. "Molecular cloning and characterization of mouse transferrin receptor 2." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33861.
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Iron (Fe) plays an essential role in numerous metabolic processes. The transferrin receptor (TfR) is a cell membrane-associated protein that serves as a gatekeeper in regulating cellular uptake of Fe from transferrin (Tf) by TfR-mediated endocytosis. TfRs are expressed ubiquitously, but their highest levels of expression are on immature erythroid cells (which are the most avid consumers of Fe in the organism) and on rapidly dividing cells, both normal and malignant. In proliferating non-erythroid cells TfR expression is feedback inhibited by Fe through the interaction of specific binding proteins, iron regulatory proteins (IRPs), with iron responsive elements (IREs) in the 3 ' untranslated region (UTR) of TfR mRNA. However, results from our lab indicate that in differentiating murine erythroleukemia (MEL) cells, TfR expression responds only slightly to an increase in intracellular Fe. An explanation for this is lacking. Importantly, a second TfR (TfR2) has recently been cloned in humans. TfR2 is highly homologous with the classical receptor, TfR1 (except for the lack of IREs in the 3' UTR), and seems to have a similar function, but shows different tissue distribution. It has been speculated that TfR2 is expressed in erythroid cells since its message is abundant in K562 cells, a human cell line that can differentiate along an erythroid lineage, and can be induced to synthesize hemoglobin. Thus, it is important to determine whether TfR2 is expressed in erythroid cells, since this could possibly explain differences in TfR regulation in erythroid vs. non-erythroid cells. In this study, I have cloned mouse TfR2 (mTfR2) by RACE (rapid amplification of cDNA ends) and sequenced it. The sequence analysis shows approximately 50% and 82% homology to mouse TfR1 and human TfR2, respectively. Tissue distribution of mTfR2, based on Northern blot analysis indicated that, in the mouse, TfR2 mRNA was predominantly expressed in the liver and its level increased about 2 fold after a
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Modun, Belinda J. "Identification and characterisation of transferrin-binding proteins in staphylococci." Thesis, University of Nottingham, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283401.
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Hsuan, J. J. "Study of the oxidation of transferrin by periodate anions." Thesis, University of Bristol, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372042.
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Ali, Stuart Alvaro. "Transferrin trojan horses : a novel approach for drug delivery?" Thesis, Brunel University, 1999. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285047.
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Araujo, Felipe Saldanha de. "Avaliação fenotípica dos linfócitos T em um modelo animal de deficiência de ferro." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/60/60135/tde-17052007-094115/.
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O ferro é um elemento chave em muitos processos metabólicos, como transporte de oxigênio, síntese de hormônios esteróides, respiração celular, transporte de elétrons, síntese de DNA, proliferação e diferenciação celular e regulação gênica. A deficiência de ferro é a desordem nutricional mais comum afetando aproximadamente um terço da população mundial. Pequenos déficits no compartimento funcional de ferro têm sérias conseqüências sobre o sistema imune, principalmente na imunidade mediada por células. A abordagem dos pais ou responsáveis, as exigências éticas e a aderência de crianças da mesma faixa etária e sem outros problemas que afetem o metabolismo do ferro e o sistema imune são as principais dificuldades enfrentadas no desenvolvimento de pesquisas com seres humanos, sendo necessário o estabelecimento de modelos experimentais. Este trabalho teve como objetivo estabelecer um modelo de indução e recuperação de deficiência de ferro em camundongos, visando a sua utilização em estudos sobre alterações do sistema imune induzidas por esta deficiência. A deficiência de ferro foi induzida por ingestão de uma ração com baixo teor de ferro (5 mg /kg de ração) por 4 e 8 semanas. No termino deste período foram determinados: concentração de hemoglobina (colorimetrico), hematócrito (microhematócrito), estoques de ferro hepático (espectrometria de absorção atômica) e fenotipagem (citometria de fluxo) dos linfócitos presentes no sangue periférico e em suspensão de células do baço dos animais dos grupos controle (C) e deficiente em ferro (DF), sendo avaliado a porcentagem de células T CD4+ e CD8+, bem como a expressão do receptor de transferrina (CD71+) nessas subpopulações. Não houve diferenças na concentração de hemoglobina e no valor do hematócrito entre os animais dos grupos DF e C, porém os estoques de ferro estavam significantemente reduzidos nos animais do grupo DF de quatro (p<0,05) e oito (p<0,01) semanas. Não houve diferenças na porcentagem de linfócitos T CD4+ e T CD8+ entre os animais dos grupos DF e C, porém os animais deficientes em ferro apresentaram maior porcentagem de linfócitos T CD8+ do baço expressando CD71+ (p< 0,001). Este trabalho sugere que a depleção nos estoques de ferro não altera a proporção dos subtipos de linfócitos, porem as células T CD8 + do baço são mais sensíveis à deficiência de ferro.Iron have a crucial role in several metabolic pathways, such oxygen transport, steroid hormone synthesis, cellular respiration, electron transport, DNA synthesis, cellular proliferation and differentiation and genic regulation. The iron deficiency is most common disorder nutrition, affecting about 30% world population. Deficits in iron functional compartment have serious delays about immunity systems, especially in the cellular immunity. Because of environmental problems, age, deficiency of nutrients other than iron, prevalence of infection, which may make human studies difficult, we used an animal model. This work aimed established iron deficiency induction and recuperation in mouse, for study about immune systems alteration. Iron deficiency was induced by feeding mice a diet that contained only 5 mg Fe/Kg for 4 and 8 weeks. After this period were determined: hemoglobin (colorimetry), hematocrit (microhematocrit), liver iron stores (atomic absorption spectrophotometer) and we performed a flow cytometry analyses in peripheral blood and spleen lymphocytes in control (C) and iron deficient (ID) mouse. We defined the effects of iron deficiency on T-cell subset and expression of cell-surface transferrin receptor (CD71+) in these cells. Hemoglobin concentration and hematocrit of ID mice were not difference those of C mice, but iron stores of ID mice (4 and 8 weeks) were reduced (p< 0,05 and p< 0,01; respectively). Although T-cells subsets in peripheral blood and spleen were not altered, iron deficiency significantly increased the number of spleen T CD8+ cells that express CD 71+ (p< 0,001). Data suggest that depletion of iron storage not alter T-cells subsets and spleen T CD8+ is the most sensible subset in iron deficiency.
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Hudson, David M. "Studies on the role of hephaestin and transferrin in iron transport." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/1491.
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Iron homeostasis is essential for maintaining the physiological requirement for iron while preventing iron overload. Multicopper ferroxidases regulate the oxidation of Fe(II) to Fe(III), circumventing the generation of harmful hydroxyl-free radicals. Ceruloplasmin is the major multicopper ferroxidase in blood; however, hephaestin, a membrane-bound ceruloplasmin homolog, has been implicated in the export of iron from duodenal enterocytes into blood. These ferroxidases supply transferrin, the iron-carrier protein in plasma, with Fe(III). Transferrin circulates through blood and delivers iron to cells via the transferrin receptor pathway. Due to the insoluble and reactive nature of free Fe(III), the oxidation of Fe(II) upon exiting the duodenal enterocyte may require an interaction between the ferroxidase and transferrin. In Chapter 3, the putative interaction of transferrin with ceruloplasmin and a soluble form of recombinant hephaestin was investigated. Utilizing native polyacrylamide gel electrophoresis, covalent cross-linking and surface plasmon resonance, a stable interaction between the two proteins was not detected. The lack of interaction between hephaestin and transferrin prompted the investigation into the localization of hephaestin in the human small intestine. Hephaestin has been reported to have both intracellular and extracellular locations in murine tissue. In the Appendix, the location of hephaestin in human tissue was investigated using a novel polyclonal antibody. Hephaestin was localized to the basolateral membrane and an intracellular location of the enterocyte, as well as a novel location in the myenteric plexus of the duodenum. The delivery of iron to cells via the transferrin receptor pathway is well established; however, little is known about the interaction of transferrin with the transferrin receptor at the molecular level. In Chapters 4 and 5, surface plasmon resonance was employed to further characterize the binding event between transferrin and the transferrin receptor. It was found that mutations affecting iron release in transferrin did not impact receptor binding. However, when N-lobe residues predicted to form contacts with the transferrin receptor were targeted, significant changes in the transferrin receptor binding kinetics and affinity were observed.
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Lokey, Laurie Kathleen. "The expression of human serum transferrin in E. Coli (Part I) : Part II: The cloning of the reverse transcriptase of human immunodeficiency virus I." Thesis, Georgia Institute of Technology, 1992. http://hdl.handle.net/1853/27380.
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Morris, Patricia Ann. "EXAFS of non-heme iron containing proteins." Diss., Georgia Institute of Technology, 1986. http://hdl.handle.net/1853/27402.
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Steinlein, Lauren Marie. "Recombinant expression of human serum transferrin in escherichia coli and pichia pastoris." Diss., Georgia Institute of Technology, 1996. http://hdl.handle.net/1853/30947.
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Zablith, Nadine. "The association between amniotic fluid albumin, prealbumin or transferrin and the fetal growth /." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98526.
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The study objectives were to measure the concentrations of albumin, prealbumin and transferrin in amniotic fluid (AF), and to establish if these concentrations were associated with infant birth weight (BW). At St Mary's Hospital (Montreal, Quebec), 294 AF samples were collected from mothers undergoing routine amniocentesis (12-19 weeks gestation). Exclusion criteria included subjects having gestational diabetes, multiple births or fetal genetic abnormalities. AF samples were analyzed by capillary electrophoresis (CE) at 190 nm. Analysis of variance and multiple linear regressions were performed. AF prealbumin could not be detected by CE. However, ANCOVA showed that transferrin was different among BW categories. Multiple regressions showed the parameter estimates for transferrin and albumin were negative, but neither was associated with BW in our study population. In contrast, transferrin was negatively associated with BW in our LBW infants. Our study shows that 2nd trimester AF transferrin may emerge as a biomarker for poor in-utero growth.
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Jordan, Peter A. "Physico-chemical studies of aluminium biochemistry." Thesis, University of East Anglia, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294654.
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Chan, Yuen-yee Roxanne. "Studies on receptor-mediated uptake of transferrin and iron acquisition by rabbit reticulocytes and a rat hepatoma cell line /." Hong Kong : University of Hong Kong, 1986. http://sunzi.lib.hku.hk/hkuto/record.jsp?B12325193.
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Koehl, Philipp. "Untersuchung von Carbohydrat-Deficient Transferrin (CDT) als Parameter für Alkoholkonsum /." Regensburg, 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000254401.
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Wiescher, Christina. "Mini-Isoelektrofokussierung von Serum-Transferrin bei Patienten mit CDG-Syndrom." Diss., lmu, 2003. http://nbn-resolving.de/urn:nbn:de:bvb:19-12684.
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Lazarus, Alan H. "Involvement of transferrin receptors in human natural killer cell specificity." Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75860.
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Natural Killer (NK) cells are able to recognize and lyse tumor cells without prior immunization or sensitization. The initial events leading to target cell lysis by NK cells involves a poorly defined recognition and binding phase. It has been hypothesized however that human NK cells may recognize transferrin receptors as target structures on tumor cells.To determine the possible involvement of transferrin receptors in human NK cell specificity, a correlation study between transferrin receptor expression and competitive activity for NK cell mediated lysis was undertaken. We have determined that the level of transferrin receptors expressed by different populations of K562 cells correlated well with their level of competitive activity for NK cell mediated lysis.
To investigate if these transferrin receptors could be recognized and bound by NK cells, a solid phase receptor binding assay was developed. As a model system, it was demonstrated that nitrocellulose immobilized transferrin retained its specific functional receptor binding capacity. This technique was quantitative and proved to be sufficiently sensitive to specifically detect nanogram quantities of transferrin receptor protein. Binding was assessed using an ELISA based system.
Human PBL were fractionated by discontinuous Percoll density centrifugation, bound to nitrocellulose, and evaluated for transferrin receptor binding capacity. A sample aliquot of cells from each Percoll fraction was retained to assess NK cell activity. It was observed that there was no positive relationship between NK cell activity and transferrin receptor binding capacity in these Percoll fractionated cells.
These findings indicate that while transferrin receptors may be involved in human NK cell specificity, they do not support a role for transferrin receptors in a high affinity mechanism between NK cells and tumor target cells.
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Sandrini, Sara M. "Interaction of Escherichia coli with catecholamine hormones, transferrin and lactoferrin." Thesis, University of Leicester, 2009. http://hdl.handle.net/2381/9946.
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The correlation between stress and increased susceptibility to infectious disease has been widely established. A direct consequence of stress, whether physical or mental, is the release of catecholamine stress hormones (adrenaline and noradrenaline), which as well as reducing immune function, have recently been shown to directly enhance the growth of a variety of Gram positive and Gram negative bacteria. The mechanism of catecholamine-induced growth stimulation involved catecholamines facilitating iron removal from the high affinity mammalian iron binding proteins transferrin and lactoferrin. In the case of Escherichia coli, the direct binding of transferrin was also an important part of this process. However, the precise mechanism(s) by which catecholamines enabled bacterial access to transferrin was not clear, and neither was the identity of the E. coli protein(s) responsible for the binding of transferrin. Using the enteropathogenic E. coli strain E2348/69 as model organism, the objectives of this project were therefore to determine how catecholamines facilitated iron removal from transferrin and lactoferrin, identify and characterise the E. coli transferrin-binding protein, and to investigate globally the effects of catecholamine stress hormones on E. coli growth and virulence. In this study, using a combination of electron paramagnetic resonance spectroscopy, chemical and polyacrylamide gel electrophoresis techniques, it was found that catecholamine stress hormones form a complex with the iron(III) associated with transferrin and lactoferrin, causing its reduction into iron(II), to which these proteins have much lower affinity. This enables the dissociation of iron from transferrin or lactoferrin, which then becomes available for bacterial uptake through ferric or ferrous iron uptake systems. It was also shown that although catecholamines enabled E. coli to acquire iron from transferrin, the amounts of iron made available by the stress hormones, while sufficient to enable growth, the levels of iron actually within the catecholamine-treated bacteria was not enough to switch off the expression of iron-regulated genes. The effects of catecholamines on expression of E. coli proteins was also investigated, and it was found that expression of intimin, important in formation of attaching and effacing lesion, was up-regulated in the presence of catecholamines. Investigation of the role of quorum sensing in the mechanism of E. coli catecholamine responsiveness was also undertaken. Analysing catecholamine responsiveness of a series of E. coli E2346/89 luxS mutants showed that luxS is not required for the ability of E. coli to interact with catecholamine stress hormones.
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Hutchinson, Carol. "Iron absorption and serum non-transferrin bound iron in humans." Thesis, King's College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.429314.
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Gordon, Harriet Mary. "Serum carbohydrate-deficient transferrin as a marker of alcohol abuse." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396017.
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Chang, Jiang. "Transferrin-PLGA nanoparticles applications to brain, glioma and trypanosoma targeting." Lille 2, 2009. http://www.theses.fr/2009LIL2S015.
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L'utilisation de nanoparticules pour la vectorisation de médicaments connaît un intérêt croissant en vue de diminuer les doses de médicaments administrés et de réduire leur toxicité. Dans le cadre de ce travail de thèse nous avons préparé des poly (D, L-lactide-co-glycolide) (PLGA) nanoparticules (NPs) biodégradables de taille de 80-nm en vue de les utiliser pour cibler les cellules surexprimant le récepteur de la transferrine (Tf-R). Lors de la préparation de ces nanoparticules nous avons montré que nous pouvions éviter l'utilisation de surfactants utilisés pour éviter l'agrégation des nanoparticules néoformées en ajoutant dans le milieu de synthèse des protéines comme la transferrine (Tf) ou la sérum albumine bovine (BSA). Ces protéines inhibent l'agrégation des nanoparticules en s'adsorbant sur leur surface. Des essais réalisés in vitro sur un modèle de la barrière hémato-encéphalique (BHE) ont montré que les Tf-NPs pouvaient pénétrer par endocytose de manière accrue et sélective la BHE en utilisant la voie des cavéoles. Les Tf-NPs activent peu le complément et ont un temps de demi-vie plasmatique chez le rat et la souris très important par rapport aux NPs seules. In vitro nous avons montré que l'endocytose de ces Tf-NPs par les cellules gliomateuses se faisait par la voie des cavéoles et que les monocytes ne les endocytosaient pas. Tous ces résultats confirment l'intérêt de tester in vivo la capacit?de ces Tf-NPs pour traiter les tumeurs cérébrales. Enfin la dernière partie de ce travail de thèse a ét?de tester l'activit?trypanocide des Tf-NPs chargées en diminazene-palmitate (DMZ-PAL). Les essais in vitro ont montré que les Tf-NPs permettaient une captation accrue des NP par trypanosoma brucei brucei (T. B. B. ) et augmentaient l'efficacité du médicament. Les essais in vivo mettent en évidence que les animaux infectés pouvaient être guéris en utilisant des doses moindres de principe actif. L'ensemble de ces résultats confirme l'intérêt de ce type de formulation pour traiter les tissus ou organes surexprimant le récepteur de la transférine
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DeRocco, Amanda Jean. "Molecular Analysis of Transferrin Binding Protein B in Neisseria Gonorrhoeae." VCU Scholars Compass, 2007. http://scholarscompass.vcu.edu/etd_retro/52.
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The transferrin iron acquisition system of Neisseria consists of two dissimilar proteins, transferrin binding protein A and B (TbpA and TbpB). TbpA and TbpB both specifically and independently bind human transferrin (Tf). TbpA is a TonB-dependent transporter, expression of which is necessary for Tf iron acquisition. In contrast, the lipoprotein TbpB is not necessary for iron internalization; however it makes this process more efficient. The role of TbpB in the transferrin iron acquisition system has not been completely elucidated. It has been suggested that TbpB is entirely surface exposed and tethered to the outer membrane by its lipid moiety. We inserted the hemagluttinin antigen (HA) epitope into TbpB in an effort to examine surface accessible and functional domains of the lipoprotein. We determined that TbpB was entirely surface exposed from just beyond the mature N-terminus. It was previously reported that the N- and C-terminus of TbpB independently bind Tf. HA epitope analysis defined both the N-terminal and C-terminal binding domains. TbpB was previously reported to play an important role in the release of Tf from the receptor. We established that TbpB exhibited a biphasic dissociation pattern; a C-terminal rapid release followed by a slower N-terminal release. These results suggested that the C-terminus plays a role in ligand turnover of the wild-type receptor. Little is known about the transport of TbpB to the outer membrane. In an attempt to identify the signals/mechanisms required for TbpB localization, the signal sequence of the protein was altered. In the absence of lipid modification, TbpB remained associated with the cell, localized to the periplasm. We also noted that internal cysteine residues were not critical for TbpB localization. Our results suggested that TbpB was transported by a lipoprotein-specific mechanism. Additionally, we demonstrated the major outer membrane secretin, PilQ, was not necessary for proper localization of TbpB. The mechanism responsible for this process remains elusive. This body of work represents the first comprehensive study of TbpB topology and function, utilizing the lipoprotein expressed in its native membrane. These results may translate to other, similar lipoprotein receptors of the pathogenic Neisseria, helping to shed light on these poorly understood proteins.
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Winsper, Sarah J. "Metal binding to transferrin and immune reactions in Parkinson's disease." Thesis, Aston University, 1995. http://publications.aston.ac.uk/11045/.
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The binding of iron (59Fe) and gallium (67Ga) to the plasma protein transferrin (Tf) was investigated by G75 gel filtration chromatography in control patients and treated and untreated patients with Parkinson's disease (PD). Fe-Tf binding was 100% in all controls and PD patients suggesting that a defect in Fe-Tf binding was not involved in the aetiology of PD. Ga-Tf binding was significantly reduced in both untreated and treated PD patients compared to controls. In addition, treated PD patients had significantly higher Ga-Tf binding than untreated patients. A reduction in metal binding to Tf could result in the increase of a low molecular weight species which may more readily enter the CNS. Alternatively, it could lead to a decrease in the transport of essential metals into the brain via the Tf receptor system. A significant elevation in neopterin was demonstrated within the plasma of untreated PD patients compared to controls suggesting the activation of a cellular immune response. Furthermore, plasma neopterin was lower in treated compared to untreated PD patients, although the difference was not significant. There was no evidence for the activation of the humoral immune response in untreated or treated PD patients as measured by circulating immune complex (CIC) levels within the plasma. An inverse relationship between Ga-Tf binding and neopterin was observed in untreated PD patients. The addition of oxidants in the form of potassium permanganate and activated manganese dioxide reduced Ga-Tf binding in control plasma. However, relatively little response was observed using monocyte preparations. The results suggest that oxidants produced by activation of the cellular immune system could damage the Tf molecule thereby reducing its ability to bind metals.
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Ghebreamlak, Weyni. "Identification of Trypsin Digested Transferrin using HPLC and MALDI-MS." Thesis, KTH, Skolan för kemi, bioteknologi och hälsa (CBH), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-266157.
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In this project, separation of trypsin digested transferrin (Tf) has been studied, using a RP HPLC- UV system equipped with a C18 column. 0.1% TFA/MQ-water and 90% MeOH were used as mobile phase A and mobile phase B, respectively. For economic reasons, the protein cytochrome c (cyt-C) was used to optimize the digestion procedure and LC system, before analysis of Tf. Four digestion methods were applied for analyzing cyt-C and Tf. The first method was digestion with no denaturing, reducing or alkylating agent. The other digestion methods used urea or heating as a denaturing agent, and lastly dithiothreitol (DTT) and iodoacetamide (IAA) as reducing and alkylating agent, respectively. The results from HPLC-UV showed that a gradient elution with a high concentration of organic solvent is favorable for the separation of cyt-C peptides. MALDI-MS was used to identify peptides, and the outcomes showed that denaturation by heat before digestion gave the best results.I detta projekt har separation av trypsin-klyvt transferrin (Tf) studerats, med användning av ett RP HPLC-UV system, som bestod av en C18 kolonn. 0,1% TFA/MQ-vatten och 90% MeOH användes som mobilfas A respektive mobilfas B. Av ekonomiska skäl användes proteinet cytokrom c (cyt-C) före analys av Tf för att optimera klyvningsprocessen och LC systemet. Fyra klyvningsmetoder studerades för analysering av cyt-C och Tf. Den första metoden innehöll inget denaturerande, reducerande eller alkylerande medel. De andra klyvningsmetoderna innehöll urea eller värme som denaturerande medel, och slutligen ditiotreitol (DTT) och jodacetamid (IAA) som reducerande respektive alkylerande medel. Resultaten från HPLC-UV visade att en gradienteluering med en hög koncentration av den organiska lösningen är gynnsam för separationen av peptiderna från cyt-C. MALDI-MS användes för att identifiera peptiderna, och resultaten visade att denaturering med värme före klyvning gav bäst resultat.