Investigating microorganisms in metal-enriched environments holds the potential to revolutionize the sustainable recovery of critical metals such as lanthanides (Ln3+). We observe Hyphomicrobium spp. as part of a Fe2+/Mn2+-oxidizing consortia native to the ferruginous bottom waters of a Ln3+-enriched lake in Czechia. Notably, one species shows similarities to recently discovered bacteria expressing proteins with picomolar Ln3+ affinity. This finding was substantiated by developing an in-silico ionic competition model and recombinant expression of a homolog protein (Hm-LanM) from Hyphomicrobium methylovorum. Biochemical assays validate Hm-LanM preference for lighter Ln3+ ions (from lanthanum to gadolinium). This is comparable to established prototypes. Bioinformatics analyses further uncover additional H. methylovorum metabolic biomolecules in genomic proximity to Hm-LanM analogously dependent on Ln3+, including an outer membrane receptor that binds Ln3+-chelating siderophores. These combined observations underscore the remarkable strategy of Hyphomicrobium spp. for thriving in relatively Ln3+ enriched zones of metal-polluted environments.
Mitochondrial autophagy (mitophagy) is very important process for the maintenance of cellular homeostasis, functionality and survival. Its dysregulation is associated with high risk and progression numerous serious diseases (e.g., oncological, neurodegenerative and cardiovascular ones). Therefore, targeting mitophagy mechanisms is very hot topic in the biological and medicinal research. The interrelationships between the regulation of mitophagy and iron homeostasis are now becoming apparent. In short, mitochondria are central point for the regulation of iron homeostasis, but change in intracellular cheatable iron level can induce/repress mitophagy. In this review, relationships between iron homeostasis and mitophagy are thoroughly discussed and described. Also, therapeutic applicability of mitophagy chelators in the context of individual diseases is comprehensively and critically evaluated.
Bordetella pertussis infects the upper airways of humans and disarms host defense by the potent immuno-subversive activities of its pertussis (PT) and adenylate cyclase (CyaA) toxins. CyaA action near-instantly ablates the bactericidal activities of sentinel CR3-expressing myeloid phagocytes by hijacking cellular signaling pathways through the unregulated production of cAMP. Moreover, CyaA-elicited cAMP signaling also inhibits the macrophage colony-stimulating factor (M-CSF)-induced differentiation of incoming inflammatory monocytes into bactericidal macrophages. We show that CyaA/cAMP signaling via protein kinase A (PKA) downregulates the M-CSF-elicited expression of monocyte receptors for transferrin (CD71) and hemoglobin-haptoglobin (CD163), as well as the expression of heme oxygenase-1 (HO-1) involved in iron liberation from internalized heme. The impact of CyaA action on CD71 and CD163 levels in differentiating monocytes is largely alleviated by the histone deacetylase inhibitor trichostatin A (TSA), indicating that CyaA/cAMP signaling triggers epigenetic silencing of genes for micronutrient acquisition receptors. These results suggest a new mechanism by which B. pertussis evades host sentinel phagocytes to achieve proliferation on airway mucosa.IMPORTANCETo establish a productive infection of the nasopharyngeal mucosa and proliferate to sufficiently high numbers that trigger rhinitis and aerosol-mediated transmission, the pertussis agent Bordetella pertussis deploys several immunosuppressive protein toxins that compromise the sentinel functions of mucosa patrolling phagocytes. We show that cAMP signaling elicited by very low concentrations (22 pM) of Bordetella adenylate cyclase toxin downregulates the iron acquisition systems of CD14+ monocytes. The resulting iron deprivation of iron, a key micronutrient, then represents an additional aspect of CyaA toxin action involved in the inhibition of differentiation of monocytes into the enlarged bactericidal macrophage cells. This corroborates the newly discovered paradigm of host defense evasion mechanisms employed by bacterial pathogens, where manipulation of cellular cAMP levels blocks monocyte to macrophage transition and replenishment of exhausted phagocytes, thereby contributing to the formation of a safe niche for pathogen proliferation and dissemination.
- MeSH
- adenylátcyklasový toxin * metabolismus genetika MeSH
- AMP cyklický * metabolismus MeSH
- antigeny CD14 * metabolismus MeSH
- antigeny diferenciační myelomonocytární MeSH
- Bordetella pertussis * MeSH
- buněčná diferenciace * MeSH
- CD antigeny metabolismus genetika MeSH
- lidé MeSH
- monocyty * metabolismus imunologie mikrobiologie MeSH
- proteinkinasy závislé na cyklickém AMP metabolismus MeSH
- receptory buněčného povrchu metabolismus genetika MeSH
- signální transdukce * MeSH
- upregulace MeSH
- železo metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Iron and copper chelation therapy plays a crucial role in treating conditions associated with metal overload, such as hemochromatosis or Wilson's disease. However, conventional chelators face challenges in reaching the core of iron and copper metabolism - the mitochondria. Mitochondria-targeted chelators can specifically target and remove metal ions from mitochondria, showing promise in treating diseases linked to mitochondrial dysfunction, including neurodegenerative diseases and cancer. Additionally, they serve as specific mitochondrial metal sensors. However, designing these new molecules presents its own set of challenges. Depending on the chelator's intended use to prevent or to promote redox cycling of the metals, the chelating moiety must possess different donor atoms and an optimal value of the electrode potential of the chelator-metal complex. Various targeting moieties can be employed for selective delivery into the mitochondria. This review also provides an overview of the current progress in the design of mitochondria-targeted chelators and their biological activity investigation.
- MeSH
- chelátory železa farmakologie MeSH
- chelátory * terapeutické užití metabolismus MeSH
- chelátová terapie metody MeSH
- lidé MeSH
- měď * metabolismus MeSH
- mitochondrie * metabolismus účinky léků MeSH
- železo * metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Arthrospira (Limnospira) maxima (A. maxima) and Chlorella vulgaris (Ch. vulgaris) are among the approved microalgae and cyanobacteria (MaC) in the food industry that are known to be safe for consumption. However, both organisms are controversial regarding their vitamin B12 content, due to the possible occurrence of pseudo-cobalamin. Concurrently, their nutrition profiles remain understudied. The main purpose of the present study was to identify their nutrition profiles, focusing mainly on vitamin B12, amino acids, and micronutrients under iron-induced hormesis (10 mg/L Fe in treated samples). Our findings indicate a higher B12 content in A. maxima compared to Ch. vulgaris (both control and treated samples). Using liquid chromatography with tandem mass spectrometry (LC-MS/MS), the cyanocobalamin content was determined as 0.42 ± 0.09 μg/g dried weight (DW) in the A. maxima control and 0.55 ± 0.02 μg/g DW in treated A. maxima, resulting in an insignificant difference. In addition, the iron-enriched medium increased the amount of iron in both tested biomasses (p < 0.01). However, a more pronounced (approximately 100×) boost was observed in Ch. vulgaris, indicating a better absorption capacity (control Ch. vulgaris 0.16 ± 0.01 mg/g Fe, treated Ch. vulgaris 15.40 ± 0.34 mg/g Fe). Additionally, Ch. vulgaris also showed a higher micronutrient content. Using both tested microalgae, meeting the sufficient recommended daily mineral allowance for an adult is possible. By combining biomass from A. maxima and Ch. vulgaris in a ratio of 6:1, we can fulfill the recommended daily allowance of vitamin B12 and iron by consuming 6 tablets/6 g. Importantly, iron hormesis stimulated amino acid composition in both organisms. The profile of amino acids may suggest these biomasses as promising potential nutrition sources.
- MeSH
- aminokyseliny * metabolismus analýza MeSH
- Chlorella vulgaris * chemie metabolismus růst a vývoj MeSH
- mikrořasy chemie metabolismus růst a vývoj MeSH
- mikroživiny * analýza metabolismus MeSH
- nutriční hodnota MeSH
- Spirulina * chemie metabolismus MeSH
- tandemová hmotnostní spektrometrie MeSH
- vitamin B 12 * metabolismus analýza MeSH
- železo metabolismus analýza MeSH
- Publikační typ
- časopisecké články MeSH
Micronutrient deficiency conditions, such as anemia, are the most prevalent global health problem due to inadequate iron and folate in dietary sources. Biofortification advancements can propel the rapid amelioration of nutritionally beneficial components in crops that are required to combat the adverse effects of micronutrient deficiencies on human health. To date, several strategies have been proposed to increase micronutrients in plants to improve food quality, but very few approaches have intrigued `clustered regularly interspaced short palindromic repeats' (CRISPR) modules for the enhancement of iron and folate concentration in the edible parts of plants. In this review, we discuss two important approaches to simultaneously enhance the bioavailability of iron and folate concentrations in rice endosperms by utilizing advanced CRISPR-Cas9-based technology. This includes the 'tuning of cis-elements' and 'enhancer re-shuffling' in the regulatory components of genes that play a vital role in iron and folate biosynthesis/transportation pathways. In particular, base-editing and enhancer re-installation in native promoters of selected genes can lead to enhanced accumulation of iron and folate levels in the rice endosperm. The re-distribution of micronutrients in specific plant organs can be made possible using the above-mentioned contemporary approaches. Overall, the present review discusses the possible approaches for synchronized iron and folate biofortification through modification in regulatory gene circuits employing CRISPR-Cas9 technology.
- MeSH
- biofortifikace * MeSH
- CRISPR-Cas systémy * MeSH
- editace genu metody MeSH
- geneticky modifikované rostliny * metabolismus genetika MeSH
- kyselina listová * metabolismus MeSH
- lidé MeSH
- rýže (rod) metabolismus genetika MeSH
- železo * metabolismus MeSH
- zemědělské plodiny * metabolismus genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Klíčová slova
- karboxymaltóza železa,
- MeSH
- ambulantní infuzní terapie MeSH
- deficit železa diagnóza etiologie MeSH
- ferritin analýza krev účinky léků MeSH
- komorbidita MeSH
- lidé MeSH
- maltosa aplikace a dávkování terapeutické užití MeSH
- srdeční selhání * etiologie patofyziologie terapie MeSH
- webová vysílání jako téma MeSH
- železité sloučeniny aplikace a dávkování terapeutické užití MeSH
- železo metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH
We explored the potential of a fungal strain Aspergillus costaricensis KS1 for modulating growth and nutrient mobilization in rice. At laboratory conditions, there was a decline in pH of the medium on inoculation with the strain and the production of citric acid was observed under broth conditions. Similarly, there was higher solubilization of tricalcium phosphate and siderophore production in liquid medium on inoculation with the strain. The effect of inoculation of KS1 was studied in rice and higher growth and yield were observed on inoculation compared to control. The content of phosphorus and iron in stem and roots of KS1 inoculated plants was higher in comparison with uninoculated control. There was also increased availability of phosphorus and iron content in soil grown with KS1 inoculated plants. In addition, inoculation with strain resulted in a higher content of volatile organic compounds such as linoleic acid, linolenic acid, and ethyl isoallocholate in stem of rice. A. costaricensis KS1 can be used for improving phosphorus and iron nutrition and impart tolerance against stresses in rice.
- MeSH
- Aspergillus * metabolismus růst a vývoj MeSH
- fosfor * metabolismus analýza MeSH
- fosforečnany vápenaté metabolismus MeSH
- koncentrace vodíkových iontů MeSH
- kořeny rostlin mikrobiologie metabolismus MeSH
- kyselina citronová metabolismus MeSH
- půdní mikrobiologie MeSH
- rýže (rod) * mikrobiologie metabolismus růst a vývoj MeSH
- siderofory * metabolismus MeSH
- stonky rostlin mikrobiologie metabolismus chemie MeSH
- těkavé organické sloučeniny * metabolismus analýza MeSH
- železo * metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
Iron is an essential mineral participating in numerous biological processes in the organism under physiological conditions. However, it may be also involved in the pathological mechanisms activated in various cardiovascular diseases including myocardial ischemia/reperfusion (I/R) injury, due to its involvement in reactive oxygen species (ROS) production. Furthermore, iron has been reported to participate in the mechanisms of iron-dependent cell death defined as "ferroptosis". On the other hand, iron may be also involved in the adaptive processes of ischemic preconditioning (IPC). This study aimed to elucidate whether small amounts of iron may modify the cardiac response to I/R in isolated perfused rat hearts and their protection by IPC. Pretreatment of the hearts with iron nanoparticles 15 min prior to sustained ischemia (iron preconditioning, Fe-PC) did not attenuate post-I/R contractile dysfunction. Recovery of left ventricular developed pressure (LVDP) was significantly improved only in the group with combined pretreatment with iron and IPC. Similarly, the rates of contraction and relaxation [+/-(dP/dt)max] were almost completely restored in the group preconditioned with a combination of iron and IPC but not with iron alone. In addition, the severity of reperfusion arrhythmias was reduced only in the iron+IPC group. No changes in protein levels of "survival" kinases of the RISK pathway (Reperfusion Injury Salvage Kinase) were found except for reduced caspase 3 levels in both preconditioned groups. The results indicate that a failure to precondition rat hearts with iron may be associated with the absent upregulation of RISK proteins and the pro-ferroptotic effect manifested by reduced glutathione peroxidase 4 (GPX4) levels. However, combination with IPC suppressed the negative effects of iron resulting in cardioprotection.
- MeSH
- ischemické přivykání * MeSH
- krysa rodu rattus MeSH
- myokard metabolismus MeSH
- potkani Wistar MeSH
- přivykání k ischémii * metody MeSH
- reperfuzní poškození myokardu * metabolismus MeSH
- srdce MeSH
- železo metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
