Search Results (32)

Four taxa of Spiraea were selected for this study: S. × cinerea Zabel ‘Grefsheim’, S. nipponica Maxim. ‘Snowmound’, S. splendens É. N. Baumann ex K. Koch and S. × vanhouttei (Briot) Carrière growing for a minimum of 5 years along heavily trafficked traffic routes. This study included the genus Spiraea due to its popularity in horticultural practice (commercial availability, widespread in urban environments). In addition, the use of ornamental shrubs for phytoremediation in urban green spaces effectively combines the aesthetic needs of residents with those of caring for the urban environment. This study was conducted in Poznań (population 550,000, the fifth largest city in Poland). Soils and foliage were examined in spring and autumn. Soil pH and specific electrolytic conductivity (EC) were determined. The content of micronutrients (Cu, Fe, Mn, Ni, Zn) and toxic heavy metals (Cd, Cr, Pb) in soil dry matter and leaves was determined. The uptake capacity of bioavailable forms of heavy metals by Spiraea from the soil was analyzed by determining the bioconcentration factor (BCF). It was found that the studied taxa meet the basic requirements for plants used for soil phytoremediation processes, especially for chromium phytoextraction. The degree of salinity of the tested soils did not pose a threat to the shrubs growing there, and most of the sites, despite the alkaline reaction, are suitable for their cultivation. S. × cinerea and S. × vanhouttei have BCFs for lead <1. The remaining taxa are characterized by strong concentrations of all analyzed elements. A particularly high BCF, above 10, was recorded for chromium and high for manganese and nickel. Full article

Understanding the role of chemokine receptors in health and disease has been of increasing interest in recent years. Chemokine receptor CXCR4 has been extensively studied because of its defined role in immune cell trafficking, HIV infection, inflammatory diseases, and cancer progression. We have developed high affinity rigidified CXCR4 antagonists that incorporate metal ions to optimize the binding interactions with the aspartate side chains at the extracellular surface of the CXCR4 chemokine receptor and increase the residence time. Cross- and side-bridged tetraazamacrocylic complexes offer significant advantages over the non-bridged molecular structures in terms of receptor affinity, potential for radiolabelling, and use in therapeutic applications. Our investigation has been extended to the influence of the ring size on bridged tetraazamacrocyclic compounds with the addition of two novel chelators (bis-cross-bridged homocyclen and bis-cross-bridged cyclen) to compare to the bis-bridged cyclam, along with novel metal complexes formed with copper(II) or zinc(II). The in vitro biological assays showed that all of the zinc(II) complexes are high affinity antagonists with a marked increase in CXCR4 selectivity for the bis-cross-bridged cyclen complex, whereas the properties of the copper(II) complexes are highly dependent on metal ion geometry. X-ray crystal structural data and DFT computational studies allow for the rationalisation of the relative affinities and the aspartate residue interactions on the protein surface. Changing the ring size from 14-membered can increase the selectivity for the CXCR4 receptor whilst retaining potent inhibitory activity, improving the key pharmacological characteristics. Full article

Copper is an essential heavy metal for diverse biological functions but toxic in excess. Consequently, a tightly regulated protein system is required to ensure adequate intracellular levels. In recent decades, several studies have explored the role of Cu⁺-ATPases in copper transport and homeostasis, revealing that these proteins are subject to kinase-mediated phosphorylation that significantly impacts their function. Techniques such as phosphoproteomic screening, site-directed mutagenesis, and artificial neural network tools demonstrated the regulatory effect of phosphorylation on these ATPases. Different protein kinases regulate Cu⁺-ATPases, modulating the active copper transport by affecting specific steps of the catalytic cycle, long-range intramolecular crosstalks, protein trafficking, gene expression, and protein stability. Therefore, the regulatory phosphorylation of Cu⁺-ATPases by kinases ultimately influences the intracellular copper distribution. This study aims to present a review of the scientific literature on the regulation of Cu⁺-ATPases by kinase-mediated phosphorylation as a crucial mechanism for copper homeostasis. This regulation offers new perspectives for developing therapies for disorders related to copper metabolism, such as Wilson and Menkes diseases, as well as cancer, diabetes mellitus, Parkinson’s, and Alzheimer’s diseases. These findings emphasize the need to further comprehend the signaling pathways involving protein kinases in the context of copper regulation. Full article

Huntington’s disease (HD) is a rare but progressive and devastating neurodegenerative disease characterized by involuntary movements, cognitive decline, executive dysfunction, and neuropsychiatric conditions such as anxiety and depression. It follows an autosomal dominant inheritance pattern. Thus, a child who has a parent with the mutated huntingtin (mHTT) gene has a 50% chance of developing the disease. Since the HTT protein is involved in many critical cellular processes, including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, and autophagy, its aberrant aggregates lead to the disruption of numerous cellular pathways and neurodegeneration. Essential heavy metals are vital at low concentrations; however, at higher concentrations, they can exacerbate HD by disrupting glial–neuronal communication and/or causing dysbiosis (disturbance in the gut microbiota, GM), both of which can lead to neuroinflammation and further neurodegeneration. Here, we discuss in detail the interactions of iron, manganese, and copper with glial–neuron communication and GM and indicate how this knowledge may pave the way for the development of a new generation of disease-modifying therapies in HD. Full article

Zinc (Zn) is the second most abundant metal in the human body and is essential for the function of 10% of all proteins. As metals cannot be synthesized or degraded, they must be assimilated from the diet by specialized transport proteins, which unfortunately also provide an entry route for the toxic metal pollutant cadmium (Cd). The intestinal absorption of Zn depends on the composition of food that is consumed, firstly the amount of Zn itself and then the quantity of other food constituents such as phytate, protein, and calcium (Ca). In cells, Zn is involved in the regulation of intermediary metabolism, gene expression, cell growth, differentiation, apoptosis, and antioxidant defense mechanisms. The cellular influx, efflux, subcellular compartmentalization, and trafficking of Zn are coordinated by transporter proteins, solute-linked carriers 30A and 39A (SLC30A and SLC39A), known as the ZnT and Zrt/Irt-like protein (ZIP). Because of its chemical similarity with Zn and Ca, Cd disrupts the physiological functions of both. The concurrent induction of a Zn efflux transporter ZnT1 (SLC30A1) and metallothionein by Cd disrupts the homeostasis and reduces the bioavailability of Zn. The present review highlights the increased mortality and the severity of various diseases among Cd-exposed persons and the roles of Zn and other transport proteins in the manifestation of Cd cytotoxicity. Special emphasis is given to Zn intake levels that may lower the risk of vision loss and bone fracture associated with Cd exposure. The difficult challenge of determining a permissible intake level of Cd is discussed in relation to the recommended dietary Zn intake levels. Full article

Zebra mussel (ZM), Dreissena polymorpha, commonly used as a sentinel species in freshwater biomonitoring, is now in competition for habitat with quagga mussel (QM), Dreissena rostriformis bugensis. This raises the question of the quagga mussel’s use in environmental survey. To better characterise QM response to stress compared with ZM, both species were exposed to cadmium (100 µg·L⁻¹), a classic pollutant, for 7 days under controlled conditions. The gill proteomes were analysed using two-dimensional electrophoresis coupled with mass spectrometry. For ZM, 81 out of 88 proteoforms of variable abundance were identified using mass spectrometry, and for QM, 105 out of 134. Interestingly, the proteomic response amplitude varied drastically, with 5.6% of proteoforms of variable abundance (DAPs) in ZM versus 9.4% in QM. QM also exhibited greater cadmium accumulation. Only 12 common DAPs were observed. Several short proteoforms were detected, suggesting proteolysis. Functional analysis is consistent with the pleiotropic effects of the toxic metal ion cadmium, with alterations in sulphur and glutathione metabolisms, cellular calcium signalling, cytoskeletal dynamics, energy production, chaperone activation, and membrane events with numerous proteins involved in trafficking and endocytosis/exocytosis processes. Beyond common responses, the sister species display distinct reactions, with cellular response to stress being the main category involved in ZM as opposed to calcium and cytoskeleton alterations in QM. Moreover, QM exhibited greater evidence of proteolysis and cell death. Overall, these results suggest that QM has a weaker stress response capacity than ZM. Full article

The objective of this research is to analyze metal elements, such as Na (sodium), Mg (magnesium), Al (aluminum), Si (silicon), Pb (lead), K (potassium), Ca (calcium), and Fe (iron), found in dust particles within two distinct areas from which the samplings were taken. The first sampling was taken from the road verge of a highly trafficked road section, while the second sampling was taken from a residential garden area 90 m away from the road. Several metal elements were detected with a high difference in Si, which presented higher concentrations in the dust samples from the road verge area. Pb has only been detected in the samples taken from the road verge, which could be explained by residual remnants from old lead gasoline and wheel weights. Additionally, during the same investigation, airborne particulate matter (PM) concentrations were measured in comparison between the road verge and the garden area; this presented a substantial difference in the concentration levels, suggesting that dense vegetation is protecting and blocking a majority of airborne PM. A literature highlight of the health effects of different metal elements and PM concentrations is presented. Full article

Among the rare earth elements (REEs), a crucial group of metals for high-technologies. Gadolinium (Gd) is the only REE intentionally injected to human patients. The use of Gd-based contrasting agents for magnetic resonance imaging (MRI) is the primary route for Gd direct exposure and accumulation in humans. Consequently, aquatic environments are increasingly exposed to Gd due to its excretion through the urinary tract of patients following an MRI examination. The increasing number of reports mentioning Gd toxicity, notably originating from medical applications of Gd, necessitates an improved risk–benefit assessment of Gd utilizations. To go beyond toxicological studies, unravelling the mechanistic impact of Gd on humans and the ecosystem requires the use of genome-wide approaches. We used functional deletomics, a robust method relying on the screening of a knock-out mutant library of Saccharomyces cerevisiae exposed to toxic concentrations of Gd. The analysis of Gd-resistant and -sensitive mutants highlighted the cell wall, endosomes and the vacuolar compartment as cellular hotspots involved in the Gd response. Furthermore, we identified endocytosis and vesicular trafficking pathways (ESCRT) as well as sphingolipids homeostasis as playing pivotal roles mediating Gd toxicity. Finally, tens of yeast genes with human orthologs linked to renal dysfunction were identified as Gd-responsive. Therefore, the molecular and cellular pathways involved in Gd toxicity and detoxification uncovered in this study underline the pleotropic consequences of the increasing exposure to this strategic metal. Full article

Due to the similarity in the basic coordination behavior of their mono-charged cations, silver biochemistry is known to be linked to that of copper in biological systems. Still, Cu⁺/²⁺ is an essential micronutrient in many organisms, while no known biological process requires silver. In human cells, copper regulation and trafficking is strictly controlled by complex systems including many cytosolic copper chaperones, whereas some bacteria exploit the so-called “blue copper” proteins. Therefore, evaluating the controlling factors of the competition between these two metal cations is of enormous interest. By employing the tools of computational chemistry, we aim to delineate the extent to which Ag⁺ might be able to compete with the endogenous copper in its Type I (T1Cu) proteins, and where and if, alternatively, it is handled uniquely. The effect of the surrounding media (dielectric constant) and the type, number, and composition of amino acid residues are taken into account when modelling the reactions in the present study. The obtained results clearly indicate the susceptibility of the T1Cu proteins to a silver attack due to the favorable composition and geometry of the metal-binding centers, along with the similarity between the Ag⁺/Cu⁺-containing structures. Furthermore, by exploring intriguing questions of both metals’ coordination chemistry, an important background for understanding the metabolism and biotransformation of silver in organisms is provided. Full article

The dual-specificity tyrosine phosphorylation-regulated kinase (DYRK1) phosphorylates diverse substrates involved in various cellular processes. Here, we found that blocking the kinase activity of DYRK1 inhibited notochord development and lumenogenesis in ascidian Ciona savignyi. By performing phosphoproteomics in conjunction with notochord-specific proteomics, we identified 1065 notochord-specific phosphoproteins that were present during lumen inflation, of which 428 differentially phosphorylated proteins (DPPs) were identified after inhibition of DYRK1 kinase activity. These DPPs were significantly enriched in metal ion transmembrane transporter activity, protein transport and localization, and tight junction. We next analyzed the downregulated phosphoproteins and focused on those belonging to the solute carrier (SLC), Ras-related protein (RAB), and tight junction protein (TJP) families. In vivo phospho-deficient study showed that alanine mutations on the phosphosites of these proteins resulted in defects of lumenogenesis during Ciona notochord development, demonstrating the crucial roles of phosphorylation of transmembrane transport-, vesicle trafficking-, and tight junction-related proteins in lumen formation. Overall, our study provides a valuable data resource for investigating notochord lumenogenesis and uncovers the molecular mechanisms of DYRK1-mediated notochord development and lumen inflation. Full article

Hydrogen sulfide has been recently identified as the third biological gasotransmitter, along with the more well studied nitric oxide (NO) and carbon monoxide (CO). Intensive studies on its potential as a therapeutic agent for cardiovascular, inflammatory, infectious and neuropathological diseases have been undertaken. Here we review the possible direct targets of H₂S in mammals. H₂S directly interacts with reactive oxygen/nitrogen species and is involved in redox signaling. H₂S also reacts with hemeproteins and modulates metal-containing complexes. Once being oxidized, H₂S can persulfidate proteins by adding -SSH to the amino acid cysteine. These direct modifications by H₂S have significant impact on cell structure and many cellular functions, such as tight junctions, autophagy, apoptosis, vesicle trafficking, cell signaling, epigenetics and inflammasomes. Therefore, we conclude that H₂S is involved in many important cellular and physiological processes. Compounds that donate H₂S to biological systems can be developed as therapeutics for different diseases. Full article

Macrophages are at the center of innate pathogen control and iron recycling. Divalent metal transporter 1 (DMT1) is essential for the uptake of non-transferrin-bound iron (NTBI) into macrophages and for the transfer of transferrin-bound iron from the endosome to the cytoplasm. As the control of cellular iron trafficking is central for the control of infection with siderophilic pathogens such as Salmonella Typhimurium, a Gram-negative bacterium residing within the phagosome of macrophages, we examined the potential role of DMT1 for infection control. Bone marrow derived macrophages lacking DMT1 (DMT1fl/fl^LysMCre(+)) present with reduced NTBI uptake and reduced levels of the iron storage protein ferritin, the iron exporter ferroportin and, surprisingly, of the iron uptake protein transferrin receptor. Further, DMT1-deficient macrophages have an impaired control of Salmonella Typhimurium infection, paralleled by reduced levels of the peptide lipocalin-2 (LCN2). LCN2 exerts anti-bacterial activity upon binding of microbial siderophores but also facilitates systemic and cellular hypoferremia. Remarkably, nifedipine, a pharmacological DMT1 activator, stimulates LCN2 expression in RAW264.7 macrophages, confirming its DMT1-dependent regulation. In addition, the absence of DMT1 increases the availability of iron for Salmonella upon infection and leads to increased bacterial proliferation and persistence within macrophages. Accordingly, mice harboring a macrophage-selective DMT1 disruption demonstrate reduced survival following Salmonella infection. This study highlights the importance of DMT1 in nutritional immunity and the significance of iron delivery for the control of infection with siderophilic bacteria. Full article

Although runoff from trafficked urban areas is recognized as a potentially significant pathway of micropollutants, runoff pollution remains poorly documented, except for relatively few historical pollutants such as some metals and hydrocarbons. Therefore, in this work, road and parking lot runoff from four sites with contrasting traffic levels were analyzed for a very broad spectrum of molecules and elements. A total of 128 pollutants and micropollutants were monitored, including inorganic (n = 41) and organic (n = 87) pollutants. Both the dissolved and particulate phases were considered. For a reduced number of samples, non-targeted screening by high-resolution mass spectrometry (HRMS) was carried out. For targeted screening, the contamination profiles were quite homogeneous, but the concentrations significantly differed between the different sites. Sites with the highest traffic density exhibited the highest concentrations for polycyclic aromatic hydrocarbons (PAHs), some traffic-related metals, alkylphenols and phthalates. Overall, for most micropollutants, the parking lot runoff exhibited the lowest concentrations, and the specificity of this site was confirmed by its HRMS fingerprint. Non-target screening allowed the sites to be discriminated based on the occurrence of specific compounds. Unlike the results of targeted screening, the HRMS intra-site variability was lower than its inter-site variability. Unknown substances were tentatively identified, either characteristic of each site or ubiquitous of all samples. Full article

The Golgi apparatus is a membrane organelle located in the center of the protein processing and trafficking pathway. It consists of sub-compartments with distinct biochemical compositions and functions. Main functions of the Golgi, including membrane trafficking, protein glycosylation, and sorting, require a well-maintained stable microenvironment in the sub-compartments of the Golgi, along with metal ion homeostasis. Metal ions, such as Ca²⁺, Mn²⁺, Zn²⁺, and Cu²⁺, are important cofactors of many Golgi resident glycosylation enzymes. The homeostasis of metal ions in the secretory pathway, which is required for proper function and stress response of the Golgi, is tightly regulated and maintained by transporters. Mutations in the transporters cause human diseases. Here we provide a review specifically focusing on the transporters that maintain Golgi metal ion homeostasis under physiological conditions and their alterations in diseases. Full article

Under abiotic stress, several changes occur in cells regarding both their physiology and cellular mechanisms. Plants have developed modifications in the production and trafficking of proteins and the remodeling of endomembranes to overcome stress conditions. The alteration in the targeting of proteins to the vacuole by shifting their transport towards an unconventional, Golgi-independent route is a good example. Plant-specific inserts (PSIs) are known to mediate such routes, and our goal was to evaluate if transgenic Arabidopsis plants overexpressing PSI B respond differently when subjected to different abiotic stresses (osmotic, oxidative, saline and by metals). The results obtained point to a differential expression of PSI B-mCherry depending on the type of stress and a decrease of cellular and cytoplasmatic movement in all stress conditions. Full article