Iron is critically important and highly regulated trace metal in the human body. However, in its free ion form, it is known to be cytotoxic; therefore, it is bound to iron storing protein, ferritin. Ferritin is a key regulator of body iron homeostasis able to form various types of minerals depending on the tissue environment. Each mineral, e.g. magnetite, maghemite, goethite, akaganeite or hematite, present in the ferritin core carry different characteristics possibly affecting cells in the tissue. In specific cases, it can lead to disease development. Widely studied connection with neurodegenerative conditions is widely studied, including Alzheimer disease. Although the exact ferritin structure and its distribution throughout a human body are still not fully known, many studies have attempted to elucidate the mechanisms involved in its regulation and pathogenesis. In this review, we try to summarize the iron uptake into the body. Next, we discuss the known occurrence of ferritin in human tissues. Lastly, we also examine the formation of iron oxides and their involvement in brain functions.
- MeSH
- ferritin metabolismus MeSH
- lidé MeSH
- mozek metabolismus MeSH
- neurodegenerativní nemoci metabolismus patologie MeSH
- oxidy metabolismus MeSH
- železo metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Environmental influences affecting genetically susceptible individuals seem to contribute significantly to the development of Parkinson's disease (PD). Xenobiotic exposure including transitional metal deposition into vulnerable CNS regions appears to interact with PD genes. Such exposure together with mitochondrial dysfunction evokes a destructive cascade of biochemical events, including oxidative stress and degeneration of the sensitive dopamine (DA) production system in the basal ganglia. Recent research indicates that the substantia nigra degeneration can be decelerated by treatment with iron binding compounds such as deferiprone. Interestingly compounds known to decrease PD risk including caffeine, niacin, nicotine and salbutamol also possess iron binding properties. Adequate function of antioxidative mechanisms in the vulnerable brain cells can be restored by acetylcysteine supplementation to normalize intracellular glutathione activity. Other preventive measures to reduce deterioration of dopaminergic neurons may involve life-style changes such as intake of natural antioxidants and physical exercise. Further research is recommended to identify therapeutic targets of the proposed interventions, in particular protection of the DA biosynthesis by oxygen radical scavengers and iron binding agents.
- MeSH
- lidé MeSH
- ochranné látky farmakologie MeSH
- Parkinsonova nemoc metabolismus prevence a kontrola MeSH
- progrese nemoci * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
A search of R. atropurpurea transcriptome for sequences encoding the transporters of the Zrt-, Irt-like Protein (ZIP) family, which are in eukaryotes integral to Zn supply into cytoplasm, allowed the identification of RaZIP1 cDNA with a predicted product belonging to ZIP I subfamily; it was subjected to functional studies in mutant Saccharomyces cerevisiae strains. The expression of RaZIP1, but not RaZIP1H208A or RaZIP1H232A mutants lacking conserved-among-ZIPs transmembrane histidyls, complemented Zn uptake deficiency in zrt1Δzrt2Δ yeasts. RaZIP1 substantially increased cellular Zn uptake in this strain and added to Zn sensitivity in zrc1Δcot1Δ mutant. The Fe uptake deficiency in ftr1Δ strain was not rescued and Mn uptake was insufficient for toxicity in Mn-sensitive pmr1Δ yeasts. By contrast, RaZIP1 increased Cd sensitivity in yap1Δ strain and conferred Cd transport activity in yeasts, albeit with substantially lower efficiency compared to Zn transport. In metal uptake assays, the accumulation of Zn in zrt1Δzrt2Δ strain remained unaffected by Cd, Fe, and Mn present in 20-fold molar excess over Zn. Immunofluorescence microscopy detected functional hemagglutinin-tagged HA::RaZIP1 on the yeast cell protoplast periphery. Altogether, these data indicate that RaZIP1 is a high-affinity plasma membrane transporter specialized in Zn uptake, and improve the understanding of the cellular and molecular biology of Zn in R. atropurpurea that is known for its ability to accumulate remarkably high concentrations of Zn.
- MeSH
- Basidiomycota genetika růst a vývoj MeSH
- biologický transport účinky léků MeSH
- fungální proteiny genetika metabolismus MeSH
- mykorhiza chemie genetika MeSH
- proteiny přenášející kationty MeSH
- regulace genové exprese u rostlin MeSH
- rostlinné proteiny chemie genetika metabolismus MeSH
- sekvence aminokyselin genetika MeSH
- zinek chemie metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Metallic biomaterial alloys composed of nickel and titanium have unique thermal shape memory, superelastic, and high damping properties, which are widely used in the medicine. The major parameter evaluated in the studies regarding the behaviour of the material in the contact with organism or cells is biocompatibility. The aim of the studies is to clarify the differences in the proliferation, growth, and morphology especially in the cell cultures. The cytotoxicity is affected among other by release of the metal ions in the presence of the metal alloy, which is further dependent on the possible treatments of the material and the corrosive properties. To evaluate the cytotoxicity, wide range of tests including the Sulforhodamine B assay and MTT tests, expression profiles, cell survival tests such as apoptotic test are used. The review compares the cell behaviour in contact with the material alloys composed of nickel and titanium with respect to different materials composition and different surface treatment that affects the ion release. Even though the results published so far are controversial, almost all data suggest sufficient biocompatibility in medical use.
- MeSH
- apoptóza účinky léků MeSH
- biokompatibilní materiály chemie farmakologie MeSH
- endoteliální buňky pupečníkové žíly (lidské) cytologie účinky léků fyziologie MeSH
- kmenové buňky cytologie účinky léků fyziologie MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- lidé MeSH
- myocyty hladké svaloviny cytologie účinky léků fyziologie MeSH
- nádorové buněčné linie MeSH
- nikl chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- rhodaminy chemie MeSH
- titan chemie farmakologie MeSH
- tuková tkáň cytologie účinky léků fyziologie MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Alzheimer's disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (Aβ) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce Aβ production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral Aβ plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.
- MeSH
- Alzheimerova nemoc dietoterapie farmakoterapie metabolismus MeSH
- lidé MeSH
- oxidační stres účinky léků MeSH
- potravní doplňky * MeSH
- sloučeniny selenu aplikace a dávkování metabolismus farmakologie terapeutické užití MeSH
- zánět farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
AfGcHK is a globin-coupled histidine kinase that is one component of a two-component signal transduction system. The catalytic activity of this heme-based oxygen sensor is due to its C-terminal kinase domain and is strongly stimulated by the binding of O2 or CO to the heme Fe(II) complex in the N-terminal oxygen sensing domain. Hydrogen sulfide (H2S) is an important gaseous signaling molecule and can serve as a heme axial ligand, but its interactions with heme-based oxygen sensors have not been studied as extensively as those of O2, CO, and NO. To address this knowledge gap, we investigated the effects of H2S binding on the heme coordination structure and catalytic activity of wild-type AfGcHK and mutants in which residues at the putative O2-binding site (Tyr45) or the heme distal side (Leu68) were substituted. Adding Na2S to the initial OH-bound 6-coordinate Fe(III) low-spin complexes transformed them into SH-bound 6-coordinate Fe(III) low-spin complexes. The Leu68 mutants also formed a small proportion of verdoheme under these conditions. Conversely, when the heme-based oxygen sensor EcDOS was treated with Na2S, the initially formed Fe(III)-SH heme complex was quickly converted into Fe(II) and Fe(II)-O2 complexes. Interestingly, the autophosphorylation activity of the heme Fe(III)-SH complex was not significantly different from the maximal enzyme activity of AfGcHK (containing the heme Fe(III)-OH complex), whereas in the case of EcDOS the changes in coordination caused by Na2S treatment led to remarkable increases in catalytic activity.
- MeSH
- biokatalýza účinky léků MeSH
- fosforylace účinky léků MeSH
- hem chemie metabolismus MeSH
- histidinkinasa chemie genetika metabolismus MeSH
- kinetika MeSH
- kyslík chemie metabolismus MeSH
- molekulární struktura MeSH
- mutageneze cílená MeSH
- Myxococcales enzymologie MeSH
- sulfan chemie farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
Russula atropurpurea can accumulate remarkably high concentrations of Zn in its sporocarps. We have previously demonstrated that 40 % of the intracellular Zn in this species is sequestered by MT-like RaZBP peptides. To see what other mechanisms for the handling of the accumulated Zn are available to R. atropurpurea, we searched its transcriptome for cDNAs coding for transporters of the cation diffusion facilitator (CDF) family. The transcriptome search enabled us to identify RaCDF1 and RaCDF2, which were further subjected to functional studies in metal sensitive Saccharomyces cerevisiae. The expression of RaCDF1 and its translational fusion with green fluorescent protein (GFP) protected the yeasts against Zn and Co, but not Cd or Mn, toxicity and led to increased Zn accumulation in the cells. The GFP fluorescence, observed in the RaCDF1::GFP-expressing yeasts on tonoplasts, indicated that the RaCDF1-mediated Zn and Co tolerance was a result of vacuolar sequestration of the metals. The expression of RaCDF2 supported Zn, but not Mn, tolerance in the yeasts and reduced the cellular uptake of Zn, which is congruent with the proposed idea of the Zn-efflux function of RaCDF2, supported by the localization of GFP-derived fluorescence on the plasma membrane of the yeasts expressing functional RaCDF2::GFP. Contrarily, RaCDF2 increased the sensitivity to Co and Cd in the yeasts and significantly promoted Cd uptake, which suggested that it can act as a bidirectional metal transporter. The notion that RaCDF1 and RaCDF2 are genuine CDF transporters in R. atropurputrea was further reinforced by the fact that the RaCDF-associated metal tolerance and uptake phenotypes were lost upon the replacement of histidyl (in RaCDF1) and aspartyl (in RaCDF2), which are highly conserved in the second transmembrane domain and known to be essential for the function of CDF proteins.
- MeSH
- aktivace transkripce MeSH
- antifungální látky farmakologie MeSH
- fungální proteiny chemie genetika metabolismus MeSH
- fyziologická adaptace MeSH
- geny hub MeSH
- kobalt farmakologie MeSH
- membránové transportní proteiny chemie genetika metabolismus MeSH
- mikrobiální testy citlivosti MeSH
- mikrobiální viabilita MeSH
- mykorhiza genetika metabolismus MeSH
- regulace genové exprese u hub MeSH
- Saccharomyces cerevisiae účinky léků růst a vývoj MeSH
- sekvence aminokyselin MeSH
- zinek metabolismus farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Macrofungi can accumulate in their sporocarps remarkably high concentrations of Cu and Ag. We have previously demonstrated that the non-essential Ag is in the ectomycorrhizal, Ag-hyperaccumulating Amanita strobiliformis sequestered by 3.4-kDa metallothioneins (MTs) produced as AsMT1a, 1b and 1c isoforms. Here, we describe two populations of wild-grown A. strobiliformis sporocarps, which showed certain correlation between the concentrations of accumulated Ag (284 ± 64 and 67 ± 15 mg kg(-1)) and Cu (76 ± 13 and 30 ± 12 mg kg(-1)), suggesting that an overlap may exist in the cell biology of Ag and Cu in this species. Metal speciation analysis revealed that the intracellular Cu in the sporocarps of both populations was, like Ag, associated with the 3.4-kDa MTs. A search of A. strobiliformis transcriptome for sequences encoding proteins of the Cu transporter (CTR) family identified four AsCTR cDNAs, which were, like AsMT1s, confirmed in both populations. The predicted AsCTR proteins showed homology to vacuolar (AsCTR1 and AsCTR4) and plasma membrane (AsCTR2 and AsCTR3) CTRs. Heterologous expression of AsCTR2, AsCTR3 and their translational fusions with green fluorescent protein (GFP) in Cu uptake-deficient S. cerevisiae indicated that both AsCTRs are functional Cu and Ag uptake transporters: recombinant genes complemented growth defects and increased Cu and Ag uptake rates in yeasts and the GFP-tagged protein localized to the cell periphery. Site directed mutagenesis revealed the importance of the conserved-among-CTRs M-X3-M motif for the AsCTR2- and AsCTR3-mediated transport of both Cu and Ag. These results provide the first evidence that fungal CTRs can recognize Ag for transport.
- MeSH
- Amanita genetika metabolismus MeSH
- exprese genu MeSH
- fungální proteiny chemie genetika metabolismus MeSH
- měď metabolismus MeSH
- membránové transportní proteiny chemie genetika metabolismus MeSH
- Saccharomyces cerevisiae MeSH
- sekvence aminokyselin MeSH
- stříbro metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The paper deals with the presence of iron-based granules in body parts of bumblebees. Two groups of bumblebees were collected from their natural habitat, industrial landscape, and from a breeding station. Detection of the magnetic particles was performed by a vibratory magnetometer and their morphology and elemental composition was analysed by scanning electron microscopy with EDX microanalysis. By means of the EDX spectra, wild bumblebees were found to have many magnetic and non-magnetic particles on their body, containing Fe, O, Al, Si, Bi, Mg, K, and Ni, likely having origin in the industrial pollution of the environment. In the case of bred bumblebees the presence of iron-rich granules, which occurred more abundantly in subsurface tissues on the head and wings, was observed. Phase analysis based on X-ray diffraction shows that iron-based granules contain magnetite and wuestite and Mössbauer spectroscopy admits a superparamagnetic form of these minerals. Magnetoreception, i.e. the sensory function of these granules, is discussed within the paper.
- MeSH
- cytoplazmatická granula metabolismus ultrastruktura MeSH
- difrakce rentgenového záření MeSH
- mikroskopie elektronová rastrovací MeSH
- spektroskopie Mossbauerova MeSH
- včely metabolismus ultrastruktura MeSH
- železo metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Iron is an essential element for fundamental cell functions and a catalyst for chemical reactions. Three samples extracted from the human spleen were investigated by scanning (SEM) and transmission electron microscopy (TEM), Mössbauer spectrometry (MS), and SQUID magnetometry. The sample with diagnosis of hemosiderosis (H) differs from that referring to hereditary spherocytosis and the reference sample. SEM reveals iron-rich micrometer-sized aggregate of various structures-tiny fibrils in hereditary spherocytosis sample and no fibrils in hemochromatosis. Hematite and magnetite particles from 2 to 6 μm in TEM with diffraction in all samples were shown. The SQUID magnetometry shows different amount of diamagnetic, paramagnetic and ferrimagnetic structures in the tissues. The MS results indicate contribution of ferromagnetically split sextets for all investigated samples. Their occurrence indicates that at least part of the sample is magnetically ordered below the critical temperature. The iron accumulation process is different in hereditary spherocytosis and hemosiderosis. This fact may be the reason of different iron crystallization.
- MeSH
- dědičná sférocytóza metabolismus patologie MeSH
- hemosideróza metabolismus patologie MeSH
- krystalizace MeSH
- lidé MeSH
- oxid železnato-železitý chemie MeSH
- pitva MeSH
- slezina chemie metabolismus patologie ultrastruktura MeSH
- spektroskopie Mossbauerova MeSH
- transmisní elektronová mikroskopie MeSH
- železité sloučeniny chemie metabolismus MeSH
- železo chemie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH