Zn Transport Research Articles

Exogenous Application of Chitosan Mitigates the Inhibitory Effects of Zinc on the Growth of Wheat Seedlings by Modulating Zn Transport and ROS Scavenging

Exogenous Application of Chitosan Mitigates the Inhibitory Effects of Zinc on the Growth of Wheat Seedlings by Modulating Zn Transport and ROS Scavenging

Citrus yellow vein clearing virus infection triggers phloem remobilization of iron- and zinc-nicotianamine in citrus.

Citrus yellow vein clearing virus (CYVCV) is a worldwide and highly destructive disease of citrus, but the mechanisms involved in CYVCV-inhibited plant growth are not well understood. This study examined nutrient levels and their cellular distribution in different organs of healthy and CYVCV-affected citrus (Citrus reticulata 'Kanpei') plants. We found that CYVCV-infected plants exhibit characteristic symptoms, including a significant reduction in iron (Fe) and other elemental nutrients in the shoots. Our data suggest that CYVCV-induced chlorosis in citrus leaf veins is primarily due to iron deficiency, leading to reduced chlorophyll synthesis. Further analysis revealed a marked decrease in iron concentration within the pith and xylem of citrus petioles post-CYVCV infection, contrasting with increased Fe and zinc (Zn) concentrations in the phloem. Moreover, a substantial accumulation of starch granules was observed in the pith, xylem, and phloem vessels of infected plants, with vessel blockage due to starch accumulation reaching up to 81%, thus significantly obstructing Fe transport in the xylem. Additionally, our study detected an upregulation of genes associated with nicotinamide metabolism and Fe and Zn transport following CYVCV infection, leading to increased levels of nicotinamide metabolites. This suggests that CYVCV-infected citrus plants may induce nicotinamide synthesis in response to Fe deficiency stress, facilitating the transport of Fe and Zn in the phloem as nicotinamide-bound complexes. Overall, our findings provide insight into the mechanisms of long-distance Fe and Zn transport in citrus plants in response to CYVCV infection and highlight the role of nutritional management in mitigating the adverse effects of CYVCV, offering potential strategies for cultivating CYVCV-resistant citrus varieties.

SENP1 mediates zinc-induced ZnT6 deSUMOylation at Lys-409 involved in the regulation of zinc metabolism in Golgi apparatus

Zinc (Zn) transporters contribute to the maintenance of intracellular Zn homeostasis in vertebrate, whose activity and function are modulated by post-translational modification. However, the function of small ubiquitin-like modifier (SUMOylation) in Zn metabolism remains elusive. Here, compared with low Zn group, a high-Zn diet significantly increases hepatic Zn content and upregulates the expression of metal-response element-binding transcription factor-1 (MTF-1), Zn transporter 6 (ZnT6) and deSUMOylation enzymes (SENP1, SENP2, and SENP6), but inhibits the expression of SUMO proteins and the E1, E2, and E3 enzymes. Mechanistically, Zn triggers the activation of the MTF-1/SENP1 pathway, resulting in the reduction of ZnT6 SUMOylation at Lys 409 by small ubiquitin-like modifier 1 (SUMO1), and promoting the deSUMOylation process mediated by SENP1. SUMOylation modification of ZnT6 has no influence on its localization but reduces its protein stability. Importantly, deSUMOylation of ZnT6 is crucial for controlling Zn export from the cytosols into the Golgi apparatus. In conclusion, for the first time, we elucidate a novel mechanism by which SUMO1-catalyzed SUMOylation and SENP1-mediated deSUMOylation of ZnT6 orchestrate the regulation of Zn metabolism within the Golgi apparatus.

Zinc/Iron-Regulated Transporter-like Protein CsZIP4 Enhances Zinc and Nitrogen Uptake and Alleviates Zinc Stresses with Nitrogen Supply in Camellia sinensis.

Zinc (Zn) and nitrogen (N) are the two crucial nutrients for tea plant growth and development and contribute to the quality formation of tea fresh leaves. In this study, a zinc/iron-regulated transporter-like protein 4 gene (i.e., CsZIP4) was functionally characterized. Expression profiling showed that CsZIP4 could be induced by Zn stresses and a N deficiency. Heterologous expression of CsZIP4 in yeast revealed that CsZIP4 possessed the capacity for Zn transport but not ammonium. Moreover, CsZIP4 overexpression in Arabidopsis thaliana promoted Zn and N uptake and transport and contributed to alleviate Zn stresses by collaborating with N supply, which might be interrelated to the expression of N or Zn metabolism-related genes, such as AtNRT1.1 and AtZIP4. Additionally, CsZIP4 was localized in the plasma membrane and chloroplast, which was helpful in maintaining cellular homeostasis under a Zn excess. Furthermore, silencing of CsZIP4 in tea plants by virus-induced gene silencing increased the chlorophyll content but decreased the Zn content. Finally, the yeast one-hybrid assay demonstrated that CsbZIP2 bound to the CsZIP4 promoter. These results will shed light on the functions of CsZIP4 in the N and Zn interaction in tea plants.

Functional carbon nanodots enhance tomato tolerance to zinc deficient soils: Mechanisms and structure-function relationships

Zinc (Zn) deficiency is a global problem disorder affecting both crops and humans. Herein, modified functional carbon nanodots (MFCNs) with various structures and characteristics were developed to regulate tomato yields and Zn migration in plant–soil systems affected by Zn deficiency through structure–function relationships. Sulfur-doped FCNs (S-FCNs), nitrogen-doped FCNs (N-FCNs), and nitrogen‑sulfur co-doped FCNs (N,S-FCNs) were hydrothermally modified using FCNs as precursors. Their regulatory effects on tomatoes growing in Zn-deficient alkaline soils were studied in pot culture experiments. Specifically, 8 mg kg−1 of FCNs and S-FCNs improved tomato yields by 132 % and 108 %, respectively, compared with the control. However, N-FCNs and N,S-FCNs showed no significant effect on yield compared with the control (P < 0.05). Moreover, the application of FCNs or S-FCNs significantly improved fruit quality and nutritional value, including Zn content (by 26.3 % and 22.0 %, respectively) and naturally occurring antioxidants (by 3.37- and 2.08-fold for lycopene, 1.31- and 1.18-fold for flavonoids, and 2.28- and 1.89-fold for phenolics, respectively; P < 0.05). Although N-FCNs and N,S-FCNs increased Zn contents, they inhibited the synthesis of naturally occurring antioxidants in fruits. Zn bioaccessibility, uptake, and transportation in plant-soil systems were regulated by MFCNs through both direct and indirect mechanisms, including ionic reactions, plant physiology, and environmental effects. MFCNs regulated plant tolerance to Zn deficiency not only by affecting root activity, redox homeostasis, micronutrient balance, chelator synthesis, genetic expression, and plant photosynthesis but also by influencing rhizosphere soil properties and the microbial environment. Based on their dual role as “plant growth regulators” and “soil conditioners”, MFCNs may have general applicability in agriculture. This study highlights the behavior of MFCNs in plant-soil systems, providing innovative nanotools for enhancing Zn availability, crop stress resistance and environmental preservation in sustainable agriculture.

Zinc Enhances Cadmium Accumulation in Shoots of Hyperaccumulator Solanum nigrum by Improving ATP-Dependent Transport and Alleviating Toxicity.

Solanum nigrum is a cadmium (Cd) and zinc (Zn) accumulator with potential for phytoextraction of soil contaminated with heavy metals. However, how Zn affects Cd accumulation in S. nigrum remains unclear. In this study, S. nigrum seedlings were treated with 100 μmol·L-1 Zn (Zn100), 100 μmol·L-1 Cd (Cd100), and the Zn and Cd combination (Zn100+Cd100) for 10 days under hydroponic culture. Compared with Cd100, the Cd content in stems, leaves, and xylem saps was 1.8, 1.6, and 1.3 times more than that in Zn100+Cd100, respectively. In addition, the production of reactive oxygen species in leaves was significantly upregulated in Cd100 compared with the control, and it was downregulated in Zn100. Comparative analyses of transcriptomes and proteomes were conducted with S. nigrum leaves. Differentially expressed genes (DEGs) were involved in Cd uptake, transport, and sequestration, and the upregulation of some transporter genes of Zn transporters (ZIPs), a natural resistance associated macrophage protein (Nramp1), a metal-nicotianamine transporter (YSL2), ATP-binding cassette transporters (ABCs), oligopeptide transporters (OPTs), and metallothionein (MTs) and glutathione S-transferase (GSTs) genes was higher in Zn100+Cd100 than in Cd100. In addition, differentially expressed proteins (DEPs) involved in electron transport chain, ATP, and chlorophyll biosynthesis, such as malate dehydrogenases (MDHs), ATPases, and chlorophyll a/b binding proteins, were mostly upregulated in Zn100. The results indicate that Zn supplement increases Cd accumulation and tolerance in S. nigrum by upregulating ATP-dependent Cd transport and sequestration pathways.

Review Article on Molecular Basis of Zinc and Copper Interactions in Cancer Physiology.

Various clinical manifestations associated with measurable abnormalities of Zn and Cu in serum and tissue were determined in Cancer-Patients (CP), and therefore, these two metals are drawing more and more attention presently than ever before. Cancer is a disease of uncontrolled-abnormal-cell-division with invasion-potential which was exhibited to occur due to dys-regulation/dys-homeostasis of fundamental-biological-pathways (FBP) including antioxidant-enzyme-defense-system, anti-inflammatory and immune-systems, and DNA-damage-repair-system in the human-body resulting in generation of chronic-oxidative-stress induced DNA-damage and gene-mutations, inflammation and compromised immune-system, tumor-induced increased angiogenesis, and inhibition of apoptosis processes. Zn and Cu were recognized to be the most crucial components of FBP and imbalance in Zn/Cu ratios in CP asserted to generate chronic toxicity in human body through various mechanisms including increased chronic oxidative stress linked compromised DNA integrity and gene mutations due to malfunctioning of DNA damage repair enzymes; increased angiogenesis process due to Zn- and Cu-binding proteins metallothionein and ceruloplasmin-induced enhanced expression of tumor growth factors; and elevation in inflammatory response which was further shown to down/upregulate gene expression of multiple Zn transporter proteins leading to dys-homeostasis of intracellular Zn concentrations, and it was determined to disturb the equilibrium between cell growth and division, proliferation, differentiation, and apoptosis processes which lead to cancer progression. Moreover, Zn was reported to affect matrix metalloproteinase activity and influence immune system cells to respond differently to different cytokines and enhance immune-suppressive effects accelerating the angiogenesis, invasion, and metastasis potential in cancer. Further, the most significant use of serum Cu/Zn ratio was recommended in clinical diagnosis, prognosis, tumor stage, patient survival, and cancer follow-up studies which need further investigations to elucidate and explore their roles in cancer physiology for clinical perspective.

Effect of the estrous cycle on zinc transporter expression in bovine cumulus-oocyte complexes and oviduct epithelial cells.

During the luteal and follicular phases of the estrous cycle, cumulus-oocyte complexes (COC) and oviduct epithelial cells (OEC) undergo notable physiological and morphological changes. Maintaining proper zinc (Zn) homeostasis is crucial in both somatic and germinal mammalian cells. This study aimed to assess the impact of the estrous phase (luteal or follicular) on Zn transporter expression in bovine COC and OEC (BOEC). The expression of Zn transporters Slc39a6 (ZIP6), Slc39a8 (ZIP8), Slc39a14 (ZIP14), Slc30a3 (ZnT3), Slc30a7 (ZnT7), and Slc30a9 (ZnT9) was analyzed in COC and BOEC from cows during the luteal or follicular phases. Gene expression of ZIP6, ZIP14, and ZnT9 was quantified in COC and BOEC. The gene expression in the remaining transporters could not be quantified due to low mRNA levels (ZIP8 and ZnT3 in COC and BOEC; ZnT7 in BOEC) or absence of expression (ZnT7 in COC). In COC, the relative expression (RE) of all three transporters was higher in the luteal phase compared to the follicular phase (P ≤ 0.05). In BOEC, the luteal phase increased the RE of ZIP 6 (P ≤ 0.05), decreased the RE of ZnT9 (P ≤ 0.05), and did not modify the RE of ZIP14 (P > 0.05) compared to the follicular phase. In conclusion, the study reveals differences in the gene expression of ZIP6, ZIP14, and ZnT9 according to the estrous cycle phase in ex vivo samples of bovine COC and OEC.

Probing Phoretic Transport of Oxidative Enzyme-Bound Zn(II)-Metallomicelle in Adenosine Triphosphate Gradient via a Spatially Relocated Biocatalytic Zone.

Although cellular transport machinery is mostly ATP-driven and ATPase-dependent, there has been a recent surge in understanding colloidal transport processes relying on a nonspecific physical interaction with biologically significant small molecules. Herein, we probe the phoretic behavior of a biocolloid [composed of a Zn(II)-coordinated metallomicelle and enzymes horseradish peroxidase (HRP) and glucose oxidase (GOx)] when exposed to a concentration gradient of ATP under microfluidic conditions. Simultaneously, we demonstrate that an ATP-independent oxidative biocatalytic product formation zone can be modulated in the presence of a (glucose + ATP) gradient. We report that both directionality and extent of transport can be tuned by changing the concentration of the ATP gradient. This diffusiophoretic mobility of a submicrometer biocolloidal object for the spatial transposition of a biocatalytic zone signifies the ATP-mediated functional transportation without the involvement of ATPase. Additionally, the ability to analyze colloidal transport in microfluidic channels using an enzymatic fluorescent product-forming reaction could be a new nanobiotechnological tool for understanding transport and spatial catalytic patterning processes. We believe that this result will inspire further studies for the realization of elusive biological transport processes and target-specific delivery vehicles, considering the omnipresence of the ATP-gradient across the cell.

ZIP11 and ZnT1 are Differentially Expressed in Human Renal Cell Carcinoma

Renal cell carcinoma (RCC) is a solid, malignant, and heterogeneous tumor originating in the renal tubular epithelium. There are several histopathological classifications, with clear-cell carcinoma (ccRCC) being the most common. Its occurrence is associated with mutations in the von Hippel-Lindau gene, which regulates cellular responses to stress, division, death, and differentiation. The loss of functionality affects the degradation of hypoxia-inducible factor (HIF). In turn, the HIF1α subunit becomes highly expressed. Zinc (Zn) is the second most abundant trace element in the human body, and small variations in its concentration can lead to disturbances in the cellular environment. Zn transporters play a fundamental role in Zn homeostasis. In this study, the expression and localization of the Zn channels ZIP11 and ZnT1 were verified in normal tubular renal cells (HK-2) and a clear cell renal adenocarcinoma line (786-0). RT-PCR and western blotting data showed that the ZIP-11 channel was highly expressed in tumor cells. In contrast, the ZnT1 channel was expressed at lower levels in tumor cells. Immunofluorescence data revealed different localization patterns between the two lines. The expression of ZIP-11 in HK-2 cells was predominantly cytoplasmic, while in 786-0 tumor cells, in addition to strong cytoplasmic staining, nuclear staining was also observed. ZnT1 expression in HK-2 cells was cytoplasmic and accentuated on the cell membrane, while that in 786-0 tumor cells was nuclear. These results demonstrated different expression patterns of the key Zn transporters, ZIP11 and ZnT1, in RCC cells compared to those in the normal kidney epithelium. Further elucidation of the molecular mechanisms underlying Zn dysregulation in RCC may reveal potential therapeutic targets.

Hydrophobic, zincophilic and conductive SEI protective layer stabilizes metallic Zn anode under high current densities

The uncontrollable growth of Zn dendrites and adverse side reactions significantly hinder the application of metallic Zn anodes in aqueous batteries. Herein, nitrogen-doped carbon skeleton/ZnO nanocrystalline are grown in-situ within carbon hollow dodecahedrons (denoted as CZCHD) through the controlled pyrolysis of zeolitic imidazole framework-8 dodecahedrons coated with polydopamine. The solid electrolyte interface layer constructed by CZCHD suppresses hydrogen evolution and corrosion reactions, reduces nucleation barrier, improves Zn deposition kinetics, accelerates desolvation and transport of Zn2+ ions, and regulates Zn deposition behavior. When tested in symmetric cells, CZCHD@Zn anodes afford exceptional plating/stripping stability at 5 mA cm−2/1 mAh cm−2 (2681 h), 10 mA cm−2/10 mAh cm−2 (780 h), and 20 mA cm−2/20 mAh cm−2 (240 h). In asymmetric cells, CZCHD@Cu exhibits average Coulombic efficiency of 99.5 % over 500 cycles. Morphological and structural evolution analyses demonstrate the preferential horizontal flaky Zn deposition beneath the CZCHD protective layer, with no Zn dendrites observed on the surface. Furthermore, when coupled with MnVO cathodes, the assembled full cells display stable cycling performance at 2 and 5 A/g. The stable, reversible, efficient, dendrite-free Zn deposition is attributed to the synergistic effects of high hydrophobicity, strong zincophilicity and high electrical conductivity of CZCHD, which is confirmed by contact angle measurements, theoretical calculations based on density functional theory, and electrochemical impedance spectroscopy.

Localization of the MTP4 transporter to trans-Golgi network in pollen tubes of Arabidopsis thaliana.

Zinc (Zn) is an essential element for plants. Numerous proteins in different cellular compartments require Zn for their structure and function. Zn can be toxic when it accumulates in high levels in the cytoplasm. Therefore, Zn homeostasis at tissue, cell, and organelle levels is vital for plant growth. A part of the metal tolerance protein (MTP) / Cation Diffusion Facilitator (CDF) transporters functions as Zn transporters, exporting Zn from the cytosol to various membrane compartments. In Arabidopsis thaliana, MTP1, MTP2, MTP3, MTP4, MTP5, and MTP12 are classified as Zn transporters (Zn-CDF). In this study, we systematically analyzed the localization of GFP-fused Zn-CDFs in the leaf epidermal cells of Nicotiana benthamiana. As previously reported, MTP1 and MTP3 were localized to tonoplast, MTP2 to endoplasmic reticulum, and MTP5 to Golgi. In addition, we identified the localization of MTP4 to trans-Golgi Network (TGN). Since MTP4 is specifically expressed in pollen, we analyzed the localization of MTP4-GFP in the Arabidopsis pollen tubes and confirmed that it is in the TGN. We also showed the Zn transport capability of MTP4 in yeast cells. We then analyzed the phenotype of an mtp4 T-DNA insertion mutant under both limited and excess Zn conditions. We found that their growth and fertility were not largely different from the wild-type. Our study has paved the way for investigating the possible roles of MTP4 in metallating proteins in the secretory pathway or in exporting excess Zn through exocytosis. In addition, our system of GFP-fused MTPs will help study the mechanisms for targeting transporters to specific membrane compartments.

Zinc proteinate with moderate chelation strength enhances zinc absorption by upregulating the expression of zinc and amino acid transporters in primary cultured duodenal epithelial cells of broiler embryos.

Recent study showed that zinc (Zn) and amino acid transporters may be involved in enhancing Zn absorption from Zn proteinate with moderate chelation strength (Zn-Prot M) in the duodenum of broilers. However, the specific mechanisms by which Zn-Prot M promotes the above Zn absorption are unknown. Therefore, in this study, 3 experiments were conducted to investigate specific and direct effects of Zn-Prot M and Zn sulfate (ZnS) on Zn absorption and expression of related transporters in primary duodenal epithelial cells of broiler embryos so as to preliminarily address possible mechanisms. In experiment 1, cells were treated with 100 μmol Zn/L as ZnS or Zn-Prot M for 20, 40, 60, 80, 100, or 120min. Experiment 2 consisted of 3 sub-experiments. In experiment 2A, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 100 or 200 μmol Zn/L as ZnS or Zn-Prot M for 60min; in experiment 2B, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 200 μmol Zn/L of as the ZnS or Zn-Prot M for 120min; in experiment 2C, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 400 or 800 μmol Zn/L as ZnS or Zn-Prot M for 120min. In experiment 3, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 400 μmol Zn/L as ZnS or Zn-Prot M for 120min. The results of experiment 1 indicated that the minimum incubation time for saturable Zn absorption was determined to be 50.83min using the best fit line. The results in experiment 2 demonstrated that a Zn concentration of 400 μmol/L and an incubation time of 120min were suitable to increase the absorption of Zn from Zn-Prot M compared to ZnS. In experiment 3, Zn absorption across cell monolayers was significantly increased by Zn addition (P < 0.05), and was significantly greater with Zn-Prot M than with ZnS (P < 0.05). Compared to the control, Zn addition significantly decreased Zn transporter 10 and peptide-transporter 1 mRNA expression levels and increased y + L-type amino transporter 2 (y + LAT2) protein abundance (P < 0.05). Moreover, protein expression levels of zrt/irt-like protein 3 (ZIP3), zrt-irt-like protein 5 (ZIP5), and y + LAT2 were significantly greater for Zn-Prot M than for ZnS (P < 0.05). These findings suggest that Zn-Prot M promote Zn absorption by increasing ZIP3, ZIP5 and y + LAT2 protein expression levels in primary duodenal epithelial cells.

Maize zinc uptake is influenced by arbuscular mycorrhizal symbiosis under various soil phosphorus availabilities.

The antagonistic interplay between phosphorus (P) and zinc (Zn) in plants is well established. However, the molecular mechanisms mediating those interactions as influenced by arbuscular mycorrhizal (AM) symbiosis remain unclear. We investigated Zn concentrations, root AM symbiosis, and transcriptome profiles of maize roots grown under field conditions upon different P levels. We also validated genotype-dependent P-Zn uptake in selected genotypes from a MAGIC population and conducted mycorrhizal inoculation experiments using mycorrhizal-defective mutant pht1;6 to elucidate the significance of AM symbiosis in P-Zn antagonism. Finally, we assessed how P supply affects Zn transporters and Zn uptake in extraradical hyphae within a three-compartment system. Elevated P levels led to a significant reduction in maize Zn concentration across the population, correlating with a marked decline in AM symbiosis, thus elucidating the P-Zn antagonism. We also identified ZmPht1;6 is crucial for AM symbiosis and confirmed that P-Zn antagonistic uptake is dependent on AM symbiosis. Moreover, we found that high P suppressed the expression of the fungal RiZRT1 and RiZnT1 genes, potentially impacting hyphal Zn uptake. We conclude that high P exerts systemic regulation over root and AM hyphae-mediated Zn uptake in maize. These findings hold implications for breeding Zn deficiency-tolerant maize varieties.

Multifunctional Roles of Zinc in Cadmium Transport in Soil-Rice Systems: Novel Insights from Stable Isotope Fractionation and Gene Expression.

The effect of Zn on Cd accumulation in rice varies under flooding and drainage conditions, and the underlying mechanism during uptake and transport from the soil to grains remains unclear. Isotope fractionation and gene expression were investigated using pot experiments under distinct water regimes and with Zn addition to gain a deeper understanding of the molecular effects of Zn on Cd uptake and transport in rice. The higher OsHMA2 expression but constitutively lower expression of zinc-regulated, iron-regulated transporter-like protein (ZIP) family genes in roots under the drainage regime than the flooding regime caused the enrichment of nonheavy Zn isotopes in the shoots relative to roots but minimally affected Cd isotopic fractionation. Drainage regime seem to exert a striking effect on the root-to-shoot translocation of Zn rather than Cd, and increased Zn transport via OsHMA2. The changes in expression patterns in response to Zn addition were similar to those observed upon switching from the flooding to drainage regime, except for OsNRAMP1 and OsNRAMP5. However, soil solution-to-rice plants and root-to-shoot fractionation toward light Zn isotopes with Zn addition (Δ66Znriceplant-soilsolution = -0.49 to -0.40‰, Δ66Znshoot-root = -0.36 to -0.27‰) indicated that Zn transport occurred via nonspecific uptake pathways and OsHMA2, respectively. Accordingly, the less pronounced and minimally varied Cd isotope fractionation suggested that OsNRAMP5 and OsHMA2 are crucial for Cd uptake and root-to-shoot transport, respectively, facilitating Cd accumulation in grains. This study demonstrated that a high Zn supply promotes Cd uptake and root-to-shoot transport in rice by sharing distinct pathways, and by utilizing a non-Zn-sensitive pathway with a high affinity for Cd.

The role of zinc and matrix metalloproteinases in myofibrillar protein degradation in critical illness myopathy

Due to an unexpected activation of different zinc (Zn) transporters in a recent prospective clinical study, we have revisited the role of Zn homeostasis and the activation of matrix metalloproteinases (MMPs) in skeletal muscle exposed to the intensive care unit (ICU) condition (immobilization and mechanical ventilation). ICU patients exposed to 12 days ICU condition were followed longitudinally with six repeated muscle biopsies while they showed a progressive preferential myosin loss, i.e., the hallmark of Critical Illness Myopathy (CIM), in parallel with the activation of Zn-transporters. In this study, we have revisited the expression of Zn-transporters and the activation of MMPs in clinical as well as in experimental studies using an established ICU model. MMPs are a group Zn-dependent endopeptidases which do not only target and cleave extracellular proteins but also intracellular proteins including multiple sarcomeric proteins. MMP-9 is of specific interest since the hallmark of CIM, the preferential myosin loss, has also been reported in dilated cardiomyopathy and coupled to MMP-9 activation. Transcriptional activation of Zn-transporters was observed in both clinical and experimental studies as well as the activation of MMPs, in particular MMP-9, in various limb and respiratory muscles in response to long-term exposure to the ICU condition. The activation of Zn-transporters was paralleled by increased Zn levels in skeletal muscle which in turn showed a negative linear correlation with the preferential myosin loss associated with CIM, offering a potential intervention strategy. Thus, activation of Zn-transporters, increased intramuscular Zn levels, and activation of the Zn-dependent MMPs are forwarded as a probable mechanism involved in CIM pathophysiology. These effects were confirmed in different rat strains subjected to a model of CIM and exacerbated by old age. This is of specific interest since old age and muscle wasting are the two factors most strongly associated with ICU mortality.

Modulation of Adverse Health Effects of Environmental Cadmium Exposure by Zinc and Its Transporters.

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.

SlZIP11 mediates zinc accumulation and sugar storage in tomato fruits.

Zinc (Zn) is a vital micronutrient essential for plant growth and development. Transporter proteins of the ZRT/IRT-like protein (ZIP) family play crucial roles in maintaining Zn homeostasis. Although the acquisition, translocation, and intracellular transport of Zn are well understood in plant roots and leaves, the genes that regulate these pathways in fruits remain largely unexplored. In this study, we aimed to investigate the function of SlZIP11 in regulating tomato fruit development. We used Solanum lycopersicum L. 'Micro-Tom' SlZIP11 (Solanum lycopersicum) is highly expressed in tomato fruit, particularly in mature green (MG) stages. For obtaining results, we employed reverse transcription-quantitative polymerase chain reaction (RT-qPCR), yeast two-hybrid assay, bimolecular fluorescent complementation, subcellular localization assay, virus-induced gene silencing (VIGS), SlZIP11 overexpression, determination of Zn content, sugar extraction and content determination, and statistical analysis. RT-qPCR analysis showed elevated SlZIP11 expression in MG tomato fruits. SlZIP11 expression was inhibited and induced by Zn deficiency and toxicity treatments, respectively. Silencing SlZIP11 via the VIGS technology resulted in a significant increase in the Zn content of tomato fruits. In contrast, overexpression of SlZIP11 led to reduced Zn content in MG fruits. Moreover, both silencing and overexpression of SlZIP11 caused alterations in the fructose and glucose contents of tomato fruits. Additionally, SlSWEEET7a interacted with SlZIP11. The heterodimerization between SlSWEET7a and SlZIP11 affected subcellular targeting, thereby increasing the amount of intracellularly localized oligomeric complexes. Overall, this study elucidates the role of SlZIP11 in mediating Zn accumulation and sugar transport during tomato fruit ripening. These findings underscore the significance of SlZIP11 in regulating Zn levels and sugar content, providing insights into its potential implications for plant physiology and agricultural practices.

Zinc transporters expression profile in professional handball players supplemented with zinc

IntroductionZinc (Zn) deficiency has been described not only on general human health but also within the sports context –as negatively affecting performance–. Thus, Zn status assessment is of great interest for athletes, especially in order to correct deficiency states of this mineral. ObjectiveThe overall objective of this work was to assess Zn status in professional handball players during the competitive period (through plasma levels, dietary intake and gene expression of the Zn transporters), as well as to determine the effect of Zn supplementation. MethodsA total of twenty-two participants were recruited, –twelve belonged to the Control Group (CG) and ten male handball players comprised the experimental group (ATH-G)–, being monitored over a 2-month period with 2 evaluation moments: baseline (i.e., initial conditions) and follow-up (i.e., after 8 weeks of training and competition). Zn intake, plasma Zn levels, and gene expression of Zn transporters were obtained. ResultsPlasma Zn levels were higher in ATH-G than in CG at the end of Zn intervention (p ≤ 0.010). Moreover, differences in the gene expression profile of Zn transporters were observed in ATH-G –with the down-regulation of several Zn transporters–, compared to the CG at baseline (p ≤ 0.05). Likewise, differences in the Zn transporters expression were observed in ATH-G at 8 weeks (all, p ≤ 0.001) –with ZnT2, ZnT5, ZIP3, ZIP5, ZIP11, ZIP13 and ZIP14 transporters being up-regulated–. ConclusionHandball players seemed to have different nutritional needs for Zn, with differences in the gene expression of Zn transporters compared to controls. Zn intervention in our athletes may have influenced the expression of Zn transporters, indicating a potential increase in Zn transporters expression to mobilize Zn at the cellular level at 8 weeks of Zn intervention.

Transcriptional regulation of Znt family members znt4, znt5 and znt10 and their function in zinc transport in yellow catfish (Pelteobagrus fulvidraco)

The study characterized the transcriptionally regulatory mechanism and functions of three zinc (Zn) transporters (znt4, znt5 and znt10) in Zn2+ metabolism in yellow catfish (Pelteobagrus fulvidraco), commonly freshwater fish in China and other countries. We cloned the sequences of znt4 promoter, spanning from −1217 bp to +80 bp relative to TSS (1297 bp); znt5, spanning from −1783 bp to +49 bp relative to TSS (1832 bp) and znt10, spanning from −1923 bp to +190 bp relative to TSS (2113 bp). In addition, after conducting the experiments of sequential deletion of promoter region and mutation of potential binding site, we found that the Nrf2 binding site (−607/−621 bp) and Klf4 binding site (−5/−14 bp) were required on znt4 promoter, the Mtf-1 binding site (−1674/−1687 bp) and Atf4 binding site (−444/−456 bp) were required on znt5 promoter and the Atf4 binding site (−905/−918 bp) was required on znt10 promoter. Then, according to EMSA and ChIP, we found that Zn2+ incubation increased DNA affinity of Atf4 to znt5 or znt10 promoter, but decreased DNA affinity of Nrf2 to znt4 promoter, Klf4 to znt4 promoter and Mtf-1 to znt5 promoter. Using fluorescent microscopy, it was revealed that Znt4 and Znt10 were located in the lysosome and Golgi, and Znt5 was located in the Golgi. Finally, we found that znt4 knockdown reduced the zinc content of lysosome and Golgi in the control and zinc-treated group; znt5 knockdown reduced the zinc content of Golgi in the control and zinc-treated group and znt10 knockdown reduced the zinc content of Golgi in the zinc-treated group. High dietary zinc supplement up-regulated Znt4 and Znt5 protein expression. Above all, for the first time, we revealed that Klf4 and Nrf2 transcriptionally regulated the activities of znt4 promoter; Mtf-1 and Atf4 transcriptionally regulated the activities of znt5 promoter and Atf4 transcriptionally regulated the activities of znt10 promoter, which provided innovative regulatory mechanism of zinc transporting in yellow catfish. Our study also elucidated their subcellular location, and regulatory role of zinc homeostasis in yellow catfish.