iron uptake Dotaz Zobrazit nápovědu
Solution chemistry of iron in biological media -- The importance of iron for biological systems -- Microbial iron transport and metabolism -- Iron uptake by plants and fungi -- Cellular iron uptake and export iron homeostasis -- Iron absorption in mammals, with particular reference to man, and regulation of systemic iron balance -- Pathophysiology of iron deficiency and iron overload in man -- Iron and oxidative between iron and other metals.
3rd ed. xx, 461 s. : il. ; 26 cm
- MeSH
- buňky metabolismus MeSH
- metabolické nemoci patofyziologie MeSH
- metaloproteiny metabolismus MeSH
- železo * metabolismus fyziologie MeSH
- Publikační typ
- monografie MeSH
We tested the effect of iron deprivation on the uptake of iron from ferric citrate by human erythroleukemia K562 cells. The iron uptake after 24-h preincubation in defined iron-free medium was approximately 2-3x higher than after the preincubation in control transferrin-containing medium. The preincubation of K562 cells in iron-free medium together with the inhibitor of protein synthesis cycloheximide completely abrogated the stimulation of the iron uptake. The preincubation in iron-free medium resulted in a slight decrease (20%) of DMT1 mRNA level. The level of Dcytb, ferroportin and hephaestin mRNA did not exert any significant change. We also did not find any significant effect on the protein level of DMT1, Dcytb, ferroportin and hephaestin. We conclude that iron deprivation stimulates the uptake of non-transferrin iron in K562 cells and that this stimulation depends on protein synthesis. It seems that the expression of an unknown or seemingly unrelated protein(s) is involved.
- MeSH
- buňky K562 MeSH
- časové faktory MeSH
- cykloheximid farmakologie MeSH
- financování organizované MeSH
- lidé MeSH
- nádorové buňky kultivované MeSH
- proteiny regulující obsah železa antagonisté a inhibitory biosyntéza MeSH
- transferin metabolismus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- železo farmakokinetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
V článku sú zhrnuté údaje o úlohe železa v interakcii baktéria – hostiteľ v súvislosti s virulenciou.Pozornosť sa venuje získavaniu železa baktériami od hostiteľa prostredníctvom nasledujúcichmechanizmov. Tieto zahrňujú získavanie železa z degradovaných produktov hemoglobínu (hém,hemín), priamo z transferínu a laktoferínu viažúceho železo, ako aj nepriamo z vyššie uvedenýchproduktov pomocou siderofórov a tiež aj z ďalších intrabunkových zdrojov (feritín). Diskutuje sa ajregulácia vychytávania železa.
Data on the role of iron in host-bacterium interaction in relation to virulence are summarized.Attention is focused on host iron acquisition pathways in bacteria. Host iron can be acquired byseveral mechanisms, e.g. from hemoglobin degradation products such as heme and hemin, directlyfrom ferrated transferrin and lactoferrin, indirectly from iron binding proteins by the productionof siderophores and from intracellular iron stores (ferritin). Regulation of iron uptake is discussed.
Myotonic dystrophy kinase-related Cdc42-binding kinase alpha (MRCKalpha, formally known as CDC42BPA) is a serine/threonine kinase that can regulate actin/myosin assembly and activity. Recently, it has been shown that it possesses a functional iron responsive element (IRE) in the 3'-untranslated region (UTR) of its mRNA, suggesting that it may be involved in iron metabolism. Here we report that MRCKalpha protein expression is also regulated by iron levels; MRCKalpha colocalizes with transferrin (Tf)-loaded transferrin receptors (TfR), and attenuation of MRCKalpha expression by a short hairpin RNA silencing construct leads to a significant decrease in Tf-mediated iron uptake. Our results thus indicate that MRCKalpha takes part in Tf-iron uptake, probably via regulation of Tf-TfR endocytosis/endosome trafficking that is dependent on the cellular cytoskeleton. Regulation of the MRCKalpha activity by intracellular iron levels could thus represent another molecular feedback mechanism cells could use to finely tune iron uptake to actual needs.
- MeSH
- endocytóza MeSH
- endozomy enzymologie MeSH
- HeLa buňky MeSH
- lidé MeSH
- malá interferující RNA genetika MeSH
- protein-serin-threoninkinasy genetika metabolismus MeSH
- receptory transferinu metabolismus MeSH
- RNA interference MeSH
- transferin metabolismus MeSH
- železo metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We investigated iron uptake mechanisms in five marine microalgae from different ecologically important phyla: the diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana, the prasinophyceae Ostreococcus tauri and Micromonas pusilla, and the coccolithophore Emiliania huxleyi. Among these species, only the two diatoms were clearly able to reduce iron, via an inducible (P. tricornutum) or constitutive (T. pseudonana) ferrireductase system displaying characteristics similar to the yeast (Saccharomyces cerevisiae) flavohemoproteins proteins. Iron uptake mechanisms probably involve very different components according to the species, but the species we studied shared common features. Regardless of the presence and/or induction of a ferrireductase system, all the species were able to take up both ferric and ferrous iron, and iron reduction was not a prerequisite for uptake. Iron uptake decreased with increasing the affinity constants of iron-ligand complexes and with increasing ligand-iron ratios. Therefore, at least one step of the iron uptake mechanism involves a thermodynamically controlled process. Another step escapes to simple thermodynamic rules and involves specific and strong binding of ferric as well as ferrous iron at the cell surface before uptake of iron. Binding was paradoxically increased in iron-rich conditions, whereas uptake per se was induced in all species only after prolonged iron deprivation. We sought cell proteins loaded with iron following iron uptake. One such protein in O. tauri may be ferritin, and in P. tricornutum, Isip1 may be involved. We conclude that the species we studied have uptake systems for both ferric and ferrous iron, both involving specific iron binding at the cell surface.
- MeSH
- autoradiografie MeSH
- biologické modely MeSH
- buněčná membrána účinky léků metabolismus MeSH
- chelátory železa farmakologie MeSH
- FMN-reduktasa metabolismus MeSH
- fylogeneze MeSH
- kinetika MeSH
- ligandy MeSH
- mikrořasy účinky léků enzymologie růst a vývoj metabolismus MeSH
- oxidace-redukce účinky léků MeSH
- Saccharomyces cerevisiae účinky léků metabolismus MeSH
- transport elektronů účinky léků MeSH
- vodní organismy růst a vývoj metabolismus MeSH
- železo metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
We have previously described a case of severe hypochromic microcytic anemia caused by a homozygous mutation in the divalent metal transporter 1 (DMT1 1285G > C). This mutation encodes for an amino acid substitution (E399D) and causes preferential skipping of exon 12 during processing of the DMT1 mRNA. To examine the functional consequences of this mutation, full-length DMT1 transcript with the patient's point mutation or a DMT1 transcript with exon 12 deleted was expressed in Chinese hamster ovary (CHO) cells. Our results demonstrate that the E399D substitution has no effect on protein expression and function. In contrast, deletion of exon 12 led to a decreased expression of the protein and disruption of its subcellular localization and iron uptake activity. We hypothesize that the residual protein in hematopoietic cells represents the functional E399D DMT1 variant, but because of its quantitative reduction, the iron uptake activity of DMT1 in the patient's erythroid cells is severely suppressed.
- MeSH
- bodová mutace MeSH
- CHO buňky MeSH
- financování organizované MeSH
- fluorescenční protilátková technika MeSH
- hypochromní anemie genetika MeSH
- křečci praví MeSH
- lidé MeSH
- proteiny přenášející kationty genetika metabolismus MeSH
- proteiny vázající železo genetika metabolismus MeSH
- transfekce MeSH
- western blotting MeSH
- železo metabolismus MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
It is well known that iron is a crucial micronutrient for all living organisms. Due to its chemical properties, iron is an irreplaceable cofactor of many essential enzymes but is also potentially toxic when present in excess. The acquisition of iron from the environment can be challenging for organisms, especially for parasitic protists that rely solely on the host for available nutrients. One of the host defense mechanisms is to starve parasites by detaining the crucial iron in a form unreachable for pathogens. In this review, we summarize current information about iron homeostasis-related pathways of important human parasites, such as Plasmodium, trypanosomes, Leishmania, pathogenic amoebas and Trichomonas. We focus on the parasites' strategies of iron acquisition, storage/detoxification, trafficking, and iron-regulated protein expression and address the questions of iron-influenced virulence and anti-parasitic chemotherapeutics targeted to iron metabolism. Finally, we outline the potential of understudied and somewhat neglected iron chelating agents as safe chemotherapeutics against protozoan parasites.
- MeSH
- biologický transport MeSH
- Entamoeba metabolismus MeSH
- lidé MeSH
- paraziti metabolismus MeSH
- Plasmodium metabolismus MeSH
- protozoální infekce parazitologie MeSH
- Trichomonadida metabolismus MeSH
- Trypanosomatina metabolismus MeSH
- železo metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
