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1.
Vet Res ; 54(1): 1, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604750

RESUMO

Streptococcus suis serotype 2 is an important bacterial pathogen of swine, responsible for substantial economic losses to the swine industry worldwide. The knowledge on the pathogenesis of the infection caused by S. suis is still poorly known. It has been previously described that S. suis possesses at least one lipoprotein with double laminin and zinc (Zn)-binding properties, which was described in the literature as either laminin-binding protein (Lmb, as in the current study), lipoprotein 103, CDS 0330 or AdcAII. In the present study, the role of the Lmb in the pathogenesis of the infection caused by S. suis serotype 2 was dissected. Using isogenic mutants, results showed that Lmb does not play an important role in the laminin-binding activity of S. suis, even when clearly exposed at the bacterial surface. In addition, the presence of this lipoprotein does not influence bacterial adhesion to and invasion of porcine respiratory epithelial and brain endothelial cells and it does not increase the susceptibility of S. suis to phagocytosis. On the other hand, the Lmb was shown to play an important role as cytokine activator when tested in vitro with dendritic cells. Finally, this lipoprotein plays a critical role in Zn acquisition from the host environment allowing bacteria to grow in vivo. The significant lower virulence of the Lmb defective mutant may be related to a combination of a lower bacterial survival due to the incapacity to acquire Zn from their surrounding milieu and a reduced cytokine activation.


Assuntos
Infecções Estreptocócicas , Streptococcus suis , Doenças dos Suínos , Animais , Suínos , Laminina/genética , Laminina/metabolismo , Sorogrupo , Citocinas/metabolismo , Células Endoteliais , Zinco/metabolismo , Infecções Estreptocócicas/veterinária , Infecções Estreptocócicas/microbiologia , Doenças dos Suínos/microbiologia
2.
Int J Mol Sci ; 24(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36674459

RESUMO

The innate immune responses of mammals to microbial infections include strategies based on manipulating the local concentration of metals such as iron (Fe) and zinc (Zn), commonly described as nutritional immunity. To evaluate whether these strategies are also present in zebrafish embryos, we have conducted a series of heart cavity-localized infection experiments with Pseudomonas aeruginosa strains characterized by a different ability to acquire Zn. We have found that, 48 h after infection, the bacterial strains lacking critical components of the Zn importers ZnuABC and ZrmABCD have a reduced colonization capacity compared to the wild-type strain. This observation, together with the finding of a high level of expression of Zur-regulated genes, suggests the existence of antimicrobial mechanisms based on Zn sequestration. However, we have observed that strains lacking such Zn importers have a selective advantage over the wild-type strain in the early stages of infection. Analysis of the expression of the gene that encodes for a Zn efflux pump has revealed that at short times after infection, P. aeruginosa is exposed to high concentrations of Zn. At the same time, zebrafish respond to the infection by activating the expression of the Zn transporters Slc30a1 and Slc30a4, whose mammalian homologs mediate a redistribution of Zn in phagocytes aimed at intoxicating bacteria with a metal excess. These observations indicate that teleosts share similar nutritional immunity mechanisms with higher vertebrates, and confirm the usefulness of the zebrafish model for studying host-pathogen interactions.


Assuntos
Pseudomonas aeruginosa , Peixe-Zebra , Animais , Pseudomonas aeruginosa/fisiologia , Peixe-Zebra/metabolismo , Eucariotos/metabolismo , Transporte de Íons , Zinco/metabolismo , Mamíferos/metabolismo
3.
Int J Mol Sci ; 24(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36674777

RESUMO

This review explains the origin of the LIV-1 family of zinc transporters, paying attention to how this family of nine human proteins was originally discovered. Structural and functional differences between these nine human LIV-1 family members and the five other ZIP transporters are examined. These differences are both related to aspects of the protein sequence, the conservation of important motifs and to the effect this may have on their overall function. The LIV-1 family are dependent on various post-translational modifications, such as phosphorylation and cleavage, which play an important role in their ability to transport zinc. These modifications and their implications are discussed in detail. Some of these proteins have been implicated in cancer which is examined. Furthermore, some additional areas of potential fruitful discovery are discussed and suggested as worthy of examination in the future.


Assuntos
Proteínas de Transporte , Proteínas de Membrana Transportadoras , Humanos , Proteínas de Transporte/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Zinco/metabolismo , Sequência de Aminoácidos
4.
Int J Mol Sci ; 24(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36675277

RESUMO

The pathogenesis of non-alcoholic fatty liver disease (NAFLD), the most prevalent chronic liver disease, is associated with zinc deficiency. Previous studies show zinc supplementation improves steatosis and glucose metabolism, but its therapeutic effects in patients with established NAFLD remain unclear. We developed an in vivo model to characterize the effects of zinc supplementation on high-fat diet (HFD) induced NAFLD and hypothesized that the established NAFLD would be attenuated by zinc supplementation. Male C57BL/6J mice were fed a control diet or HFD for 12 weeks. Mice were then further grouped into normal and zinc-supplemented diets for 8 additional weeks. Body composition and glucose tolerance were determined before and after zinc supplementation. At euthanasia, plasma and liver tissue were collected for characterization and downstream analysis. As expected, 12 weeks of HFD resulted in reduced glucose clearance and altered body composition. Eight weeks of subsequent zinc supplementation did not alter glucose handling, plasma transaminases, steatosis, or hepatic gene expression. Results from our model suggest 8-week zinc supplementation cannot reverse established NAFLD. The HFD may have caused NAFLD disease progression beyond rescue by an 8-week period of zinc supplementation. Future studies will address these limitations and provide insights into zinc as a therapeutic agent for established NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Masculino , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Dieta Hiperlipídica/efeitos adversos , Zinco/metabolismo , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Suplementos Nutricionais , Glucose/metabolismo , Modelos Animais de Doenças
5.
Planta ; 257(2): 44, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690717

RESUMO

MAIN CONCLUSION: Zinc deficiency altered shoot and root growth, plant biomass, yield, and ZIP family transporter gene expression in sorghum. Zinc (Zn) deficiency affects several crop plants' growth and yield, including sorghum. We have evaluated the sorghum under various concentrations of Zn supply for phenotypic changes, Zn content, and expression of Zn-regulated, iron-regulated transporter-like proteins (ZIP) family genes. Zn deficiency reduced the shoot and root growth, plant biomass, and yield by > 50%. The length and number of lateral roots were increased by more than 50% under deficient Zn compared to sufficient Zn. Ten SbZIP family transporter genes showed dynamic expression in shoot and root tissues of sorghum under deficient and sufficient Zn. SbZIP2, 5, 6, 7, and 8 were expressed in all tissues under deficient and sufficient Zn. SbZIP2, 4, 5, 6, 7, 8, and 10 were highly induced in shoot tissues by deficient Zn. The expression level of SbZIP6, 7, 8, and 9 was higher in root tissues under deficient Zn. The phylogenetic analysis revealed that most SbZIP family proteins are closely associated with the ZmZIP family of maize. The functional residues His177 and Gly182 are fully conserved in all SbZIP family transporters, as revealed by homology modeling and multiple sequence alignment. This study may provide a foundation for improving the Zn-use efficiency of sorghum.


Assuntos
Sorghum , Zinco , Zinco/metabolismo , Sorghum/metabolismo , Filogenia , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Grão Comestível/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Raízes de Plantas/metabolismo
6.
Mol Cell ; 83(2): 252-265.e13, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36630955

RESUMO

The conserved regulon of heat shock factor 1 in budding yeast contains chaperones for general protein folding as well as zinc-finger protein Zpr1, whose essential role in archaea and eukaryotes remains unknown. Here, we show that Zpr1 depletion causes acute proteotoxicity driven by biosynthesis of misfolded eukaryotic translation elongation factor 1A (eEF1A). Prolonged Zpr1 depletion leads to eEF1A insufficiency, thereby inducing the integrated stress response and inhibiting protein synthesis. Strikingly, we show by using two distinct biochemical reconstitution approaches that Zpr1 enables eEF1A to achieve a conformational state resistant to protease digestion. Lastly, we use a ColabFold model of the Zpr1-eEF1A complex to reveal a folding mechanism mediated by the Zpr1's zinc-finger and alpha-helical hairpin structures. Our work uncovers the long-sought-after function of Zpr1 as a bespoke chaperone tailored to the biogenesis of one of the most abundant proteins in the cell.


Assuntos
Proteínas de Transporte , Chaperonas Moleculares , Proteínas de Transporte/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Biossíntese de Proteínas , Zinco/metabolismo , Dedos de Zinco , Fator 1 de Elongação de Peptídeos/metabolismo
7.
J Inorg Biochem ; 240: 112117, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36635196

RESUMO

A systematic study of the effect of phosphine and bis-phosphine ligands in the interaction of NiII, PdII, and PtII complexes with two classes of zinc fingers was performed. The Cys2His2, finger 3 of specific protein-1, and the Cys2HisCys C-terminal zinc finger of nucleocapsid protein 7 of the HIV-1 were used as models of the respective class. In general, phosphine ligands favor the metal binding to the peptide, although the bis-phosphine ligands produce more specific binding than the monodentate. In the case of nickel complexes, the interaction of NiII ions with the sequence SKH, present in Cys2His2, results in hydrolysis, contrasting to the preferred zinc ejection produced by the NiII complexes with chelating phosphines, producing Ni(bis-phosphine) fingers. In the absence of the SKH sequence, zinc ejection is observed with the formation of nickel fingers, with reactivity dependent on the phosphine. On the other hand, Pd(phosphines) produces Pd2 fingers in the case of triphenylphosphine with the phosphine coordinated as intermediate species. The bis-phosphine ligands produce very clean spectra and a stable signal Pd(bis-phosphine)finger. Interestingly, phosphines produce very reactive platinum complexes, which eject zinc and promote peptide hydrolysis. The results reported here are relevant to the understanding of the mechanism of these interactions and how to modulate metallocompounds for zinc finger interference.


Assuntos
Fosfinas , Fosfinas/química , Níquel , Ligantes , Hidrólise , Dedos de Zinco , Zinco/metabolismo
8.
Nat Commun ; 14(1): 385, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693843

RESUMO

The Zrt-/Irt-like protein (ZIP) family consists of ubiquitously expressed divalent metal transporters critically involved in maintaining systemic and cellular homeostasis of zinc, iron, and manganese. Here, we present a study on a prokaryotic ZIP from Bordetella bronchiseptica (BbZIP) by combining structural biology, evolutionary covariance, computational modeling, and a variety of biochemical assays to tackle the issue of the transport mechanism which has not been established for the ZIP family. The apo state structure in an inward-facing conformation revealed a disassembled transport site, altered inter-helical interactions, and importantly, a rigid body movement of a 4-transmembrane helix (TM) bundle relative to the other TMs. The computationally generated and biochemically validated outward-facing conformation model revealed a slide of the 4-TM bundle, which carries the transport site(s), by approximately 8 Å toward the extracellular side against the static TMs which mediate dimerization. These findings allow us to conclude that BbZIP is an elevator-type transporter.


Assuntos
Proteínas de Bactérias , Proteínas de Transporte de Cátions , Proteínas de Bactérias/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Metais/metabolismo , Zinco/metabolismo , Ferro/metabolismo
9.
BMC Plant Biol ; 23(1): 20, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627574

RESUMO

Although the interaction between P and Zn has long been recognized in plants, the physiological and molecular mechanisms underlying P and Zn interactions are poorly understood. We show here that P supply decreases the Zn concentration in maize shoots and roots. Compared to +P + Zn (addition of both P and Zn), +P-Zn reduced and -P-Zn increased the total length of 1° lateral roots (LRs). Under +P + Zn, both P and Zn concentrations were lower in the sl1 mutant roots than in wild-type (WT) maize roots, and P accumulation did not reduce the Zn concentration in ll1 mutant roots. Transcriptome profiling showed that the auxin signaling pathway contributed to P-mediated Zn homeostasis in maize. Auxin production and distribution were altered by changes in P and Zn supply. Cytosolic Zn co-localized with auxin accumulation under +P + Zn. Exogenous application of 1-NAA and L-Kyn altered the P-mediated root system architecture (RSA) under Zn deficiency. -P-Zn repressed the expression of miR167. Overexpression of ZmMIR167b increased the lengths of 1° LRs and the concentrations of P and Zn in maize. These results indicate that auxin-dependent RSA is important for P-mediated Zn homeostasis in maize.HighlightAuxin-dependent RSA is important for P-mediated Zn homeostasis in maize.


Assuntos
Fósforo , Zea mays , Fósforo/metabolismo , Zea mays/metabolismo , Raízes de Plantas/metabolismo , Ácidos Indolacéticos/metabolismo , Homeostase , Zinco/metabolismo , Transdução de Sinais
10.
Sci Rep ; 13(1): 676, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635301

RESUMO

Micronutrient deficiencies such as iron (Fe), zinc (Zn), and vitamin A, constitute a severe global public health phenomenon. Over half of preschool children and two-thirds of nonpregnant women of reproductive age worldwide have micronutrient deficiencies. Biofortification is a cost-effective strategy that comprises a meaningful and sustainable means of addressing this issue by delivering micronutrients through staple foods to populations with limited access to diverse diets and other nutritional interventions. Here, we report on the proof-of-concept and early development stage of a collection of biofortified rice events with a high density of Fe and Zn in polished grains that have been pursued further to advance development for product release. In total, eight constructs were developed specifically expressing dicot ferritins and the rice nicotianamine synthase 2 (OsNAS2) gene under different combinations of promoters. A large-scale transformation of these constructs to Bangladesh and Philippines commercial indica cultivars and subsequent molecular screening and confined field evaluations resulted in the identification of a pool of ten events with Fe and Zn concentrations in polished grains of up to 11 µg g-1 and up to 37 µg g-1, respectively. The latter has the potential to reduce the prevalence of inadequate Zn intake for women of childbearing age in Bangladesh and in the Philippines by 30% and 50%, respectively, compared to the current prevalence. To our knowledge, this is the first potential biotechnology public-sector product that adopts the product cycle phase-gated approach, routinely applied in the private sector.


Assuntos
Oryza , Ferritinas/genética , Ferro/metabolismo , Micronutrientes , Compostos Orgânicos , Oryza/química , Zinco/metabolismo , Plantas Geneticamente Modificadas
11.
BMC Microbiol ; 23(1): 6, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36617571

RESUMO

The control of cellular zinc (Zn) concentrations by dedicated import and export systems is essential for the survival and virulence of Pseudomonas aeruginosa. The transcription of its many Zn transporters is therefore tightly regulated by a known set of transcription factors involved in either the import or the export of Zn. In this work, we show that the Zur protein, a well-known repressor of Zn import, plays a dual role and functions in both import and export processes. In a situation of Zn excess, Zur represses Zn entry, but also activates the transcription of czcR, a positive regulator of the Zn export system. To achieve this, Zur binds at two sites, located by DNA footprinting in the region downstream the czcR transcription start site. In agreement with this regulation, a delay in induction of the efflux system is observed in the absence of Zur and Zn resistance is reduced. The discovery of this regulation highlights a new role of Zur as global regulator of Zn homeostasis in P. aeruginosa disclosing an important link between Zur and zinc export.


Assuntos
Pseudomonas aeruginosa , Zinco , Zinco/metabolismo , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Fatores de Transcrição/genética
12.
Virulence ; 14(1): 2156196, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36482737

RESUMO

Metals are nutrients essential for almost all lifeforms. Bacteria have evolved several mechanisms to overcome the metal restrictions imposed by the host. Vibrio parahaemolyticus causes severe threats to public health and significant economic losses in shrimp aquaculture. Herein, we report that ZrgA contributes to zinc acquisition in this pathogen. The operon VP_RS01455 to VP_RS01475 of V. parahaemolyticus encodes the putative Zn transporter ZrgABCDE, whose homologs are widely distributed in Vibrionaceae. RNA sequencing analysis revealed that V. parahaemolyticus modulates the transcriptome in response to Zn limitation. Genes in the Zinc uptake regulator (Zur) regulon are upregulated during Zn limitation, including three genes annotated to encode Zn-binding proteins. Significant upregulation of these three genes during Zn limitation was also confirmed by quantitative real-time PCR (qRT-PCR) analysis. However, only the mutants containing a VP_RS01470 (zrgA) deletion exhibited impaired growth under Zn-deficient conditions, indicating that VP_RS01470 plays the predominant role in V. parahaemolyticus Zn acquisition. The VP_RS01470 deletion mutant displayed a false appearance of decreased swimming motility under Zn-deficient conditions, as revealed by the fact that the polar flagellar-related genes were not downregulated in the mutant. Moreover, VP_RS01470 deletion produced no noticeable impact on the swarming motility and virulence in mice. qRT-PCR analysis and ß-galactosidase activity assays indicated that Zur negatively regulates VP_RS01470 expression in V. parahaemolyticus. Collectively, our findings suggest that ZrgA is required for Zn acquisition in V. parahaemolyticus and highlight the importance of detecting the expression of flagellar genes during analysis of motility of a mutant deficient in growth.


Assuntos
Vibrio parahaemolyticus , Animais , Camundongos , Vibrio parahaemolyticus/genética , Zinco/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Transporte/metabolismo , Transcriptoma , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
13.
J Health Econ ; 87: 102691, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36521402

RESUMO

We examine the negative child health impacts of soil zinc (Zn) deficiency in Nepal. Soil Zn deficiency limits both crop yields and the Zn concentration in food crops, leading many to speculate that it underlies human Zn deficiency and child stunting, globally and particularly in South Asia. We find strong evidence that soil Zn deficiency does have a causal impact on child stunting in Nepal's Tarai region, the breadbasket of the country. Using causal bounds, we find that a 1 part per million increase in plant-available soil Zn - achievable with application of Zn-enriched fertilizer - decreases child stunting by between 1 and 7.5 percentage points. Multiple statistical sensitivity tests indicate that this relationship is unlikely to be manufactured by omitted, relevant variables.


Assuntos
Solo , Zinco , Criança , Humanos , Nepal/epidemiologia , Zinco/análise , Zinco/metabolismo , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/etiologia
14.
Chemosphere ; 313: 137447, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36509194

RESUMO

This study aimed to investigate the combined ecotoxicological effects of Cd, Pb, Zn, Hg and regulation mechanisms in Solanum nigrum L. In this work, the co-exposure of these four heavy metals hindered the transformation of Cd, Zn, and Hg (except Pb) from available to non-available chemical forms. Individual Cd, Pb, Zn and Hg induced the oxidative damages to S. nigrum L., while their combination further enhanced this ecological toxicity. By internal regulation, the ecological toxicity of metals to S. nigrum L. could be alleviated to a certain extent. Specifically, S. nigrum L. was a hyperaccumulator of Cd with BCF >1. Moreover, since BCFroot of Pb, Zn and Hg were all greater than BCFshoot, S. nigrum L. could accumulate Pb, Hg and Zn mainly in plant roots, which was beneficial for the detoxification of plants. Meanwhile, the immobilization by cell wall (the proportions of Cd, Pb, Zn and Hg in the cell wall were 54.46-84.92%, 38.33-49.25%, 48.38-56.19% and 45.97-63.47% in low metal concentration treatments) and the sequestration in vacuole (the proportions of Cd, Pb, Zn, and Hg in the soluble fractions are 50.99-59.00%, 41.05-45.46%, 37.54-61.04% and 33.47-61.35% in high metal concentration treatments) also act as important detoxification pathways. The external regulation was mainly the changes of soil microbial communities influenced by plants. Specifically, the richness and diversity of bacteria in rhizosphere soil were increased, and roots of S. nigrum L. recruited some potentially beneficial microbials. This study provided a theoretical basis and guidance for S. nigrum L. as a phytoremediation plant under combined heavy metal pollution.


Assuntos
Mercúrio , Metais Pesados , Poluentes do Solo , Solanum nigrum , Cádmio/análise , Solanum nigrum/metabolismo , Chumbo/metabolismo , Metais Pesados/análise , Mercúrio/metabolismo , Solo , Zinco/metabolismo , Poluentes do Solo/análise , Biodegradação Ambiental
15.
Mol Cancer ; 21(1): 229, 2022 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-36581942

RESUMO

RATIONALE: Lung cancer is the most prevalent form of cancer and has a high mortality rate, making it a global public health concern. The N6-methyladenosine (m6A) modification is a highly dynamic and reversible process that is involved in a variety of essential biological processes. Using in vitro, in vivo, and multi-omics bioinformatics, the present study aims to determine the function and regulatory mechanisms of the long non-coding (lnc)RNA zinc ribbon domain-containing 1-antisense 1 (ZNRD1-AS1). METHODS: The RNAs that were bound to the m6A 'reader' were identified using YTH domain-containing 2 (YTHDC2) RNA immunoprecipitation (RIP)-sequencing. Utilizing methylated RIP PCR/quantitative PCR, pull-down, and RNA stability assays, m6A modification and ZNRD1-AS1 regulation were analyzed. Using bioinformatics, the expression levels and clinical significance of ZNRD1-AS1 in lung cancer were evaluated. Using fluorescent in situ hybridization and quantitative PCR assays, the subcellular location of ZNRD1-AS1 was determined. Using cell migration, proliferation, and angiogenesis assays, the biological function of ZNRD1-AS1 in lung cancer was determined. In addition, the tumor suppressor effect of ZNRD1-AS1 in vivo was validated using a xenograft animal model. Through bioinformatics analysis and in vitro assays, the downstream microRNAs (miRs) and competing endogenous RNAs were also predicted and validated. RESULTS: This study provided evidence that m6A modification mediates YTHDC2-mediated downregulation of ZNRD1-AS1 in lung cancer and cigarette smoke-exposed cells. Low levels of ZNRD1-AS1 expression were linked to adverse clinicopathological characteristics, immune infiltration, and prognosis. ZNRD1-AS1 overexpression was shown to suppress lung cancer cell proliferation, migration, and angiogenesis in vitro and in vivo, and to reduce tumor growth in nude mice. ZNRD1-AS1 expression was shown to be controlled by treatment of cells with either the methylation inhibitor 3-Deazaadenosine or the demethylation inhibitor Meclofenamic. Furthermore, the miR-942/tensin 1 (TNS1) axis was demonstrated to be the downstream regulatory signaling pathway of ZNRD1-AS1. CONCLUSIONS: ZNRD1-AS1 serves an important function and has clinical relevance in lung cancer. In addition, the findings suggested that m6A modification could mediate the regulation of the ZNRD1-AS1/miR-942/TNS1 axis via the m6A reader YTHDC2.


Assuntos
Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Animais , Camundongos , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Camundongos Nus , Zinco/metabolismo , Hibridização in Situ Fluorescente , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pulmonares/genética , Movimento Celular/genética , Pulmão/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , RNA Helicases/genética , Tensinas/genética , Tensinas/metabolismo
16.
Nucleic Acids Res ; 50(22): 12739-12753, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36533433

RESUMO

Bacteria can adapt in response to numerous stress conditions. One such stress condition is zinc depletion. The zinc-sensing transcription factor Zur regulates the way numerous bacterial species respond to severe changes in zinc availability. Under zinc sufficient conditions, Zn-loaded Zur (Zn2-Zur) is well-known to repress transcription of genes encoding zinc uptake transporters and paralogues of a few ribosomal proteins. Here, we report the discovery and mechanistic basis for the ability of Zur to up-regulate expression of the ribosomal protein L31 in response to zinc in E. coli. Through genetic mutations and reporter gene assays, we find that Zur achieves the up-regulation of L31 through a double repression cascade by which Zur first represses the transcription of L31p, a zinc-lacking paralogue of L31, which in turn represses the translation of L31. Mutational analyses show that translational repression by L31p requires an RNA hairpin structure within the l31 mRNA and involves the N-terminus of the L31p protein. This work uncovers a new genetic network that allows bacteria to respond to host-induced nutrient limiting conditions through a sophisticated ribosomal protein switching mechanism.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Regulação Bacteriana da Expressão Gênica , Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , RNA/metabolismo , Zinco/farmacologia , Zinco/metabolismo , Interações entre Hospedeiro e Microrganismos
17.
Int J Mol Sci ; 23(24)2022 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-36555806

RESUMO

Zinc is an important trace mineral in the human body and a daily intake of zinc is required to maintain a healthy status. Over the past decades, zinc has been used in formulating topical and systemic therapies for various skin disorders owing to its wound healing and antimicrobial properties. Zinc transporters play a major role in maintaining the integrity of the integumentary system by controlling zinc homeostasis within dermal layers. Mutations and abnormal function of zinc-transporting proteins can lead to disease development, such as spondylocheirodysplastic Ehlers-Danlos syndrome (SCD-EDS) and acrodermatitis enteropathica (AE) which can be fatal if left untreated. This review discusses the layers of the skin, the importance of zinc and zinc transporters in each layer, and the various skin disorders caused by zinc deficiency, in addition to zinc-containing compounds used for treating different skin disorders and skin protection.


Assuntos
Acrodermatite , Dermatologia , Dermatopatias , Humanos , Pele/metabolismo , Acrodermatite/tratamento farmacológico , Dermatopatias/metabolismo , Zinco/metabolismo
18.
Int J Mol Sci ; 23(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36555178

RESUMO

Ros/MucR is a widespread family of bacterial zinc-finger-containing proteins that integrate multiple functions, such as symbiosis, virulence, transcription regulation, motility, production of surface components, and various other physiological processes in cells. This regulatory protein family is conserved in bacteria and is characterized by its zinc-finger motif, which has been proposed as the ancestral domain from which the eukaryotic C2H2 zinc-finger structure has evolved. The first prokaryotic zinc-finger domain found in the transcription regulator Ros was identified in Agrobacterium tumefaciens. In the past decades, a large body of evidence revealed Ros/MucR as pleiotropic transcriptional regulators that mainly act as repressors through oligomerization and binding to AT-rich target promoters. The N-terminal domain and the zinc-finger-bearing C-terminal region of these regulatory proteins are engaged in oligomerization and DNA binding, respectively. These properties of the Ros/MucR proteins are similar to those of xenogeneic silencers, such as H-NS, MvaT, and Lsr2, which are mainly found in other lineages. In fact, a novel functional model recently proposed for this protein family suggests that they act as H-NS-'like' gene silencers. The prokaryotic zinc-finger domain exhibits interesting structural and functional features that are different from that of its eukaryotic counterpart (a ßßßα topology), as it folds in a significantly larger zinc-binding globular domain (a ßßßαα topology). Phylogenetic analysis of Ros/MucR homologs suggests an ancestral origin of this type of protein in α-Proteobacteria. Furthermore, multiple duplications and lateral gene transfer events contributing to the diversity and phyletic distribution of these regulatory proteins were found in bacterial genomes.


Assuntos
Proteínas de Bactérias , Dedos de Zinco , Filogenia , Sequência de Aminoácidos , Proteínas de Bactérias/metabolismo , Dedos de Zinco/genética , Fatores de Transcrição/genética , Bactérias/metabolismo , Zinco/metabolismo
19.
Int J Mol Sci ; 23(24)2022 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-36555788

RESUMO

The muscleblind-like protein family (MBNL) plays a prominent role in the regulation of alternative splicing. Consequently, the loss of MBNL function resulting from sequestration by RNA hairpins triggers the development of a neuromuscular disease called myotonic dystrophy (DM). Despite the sequence and structural similarities between the four zinc-finger domains that form MBNL1, recent studies have revealed that the four binding domains have differentiated splicing activity. The dynamic behaviors of MBNL1 ZnFs were simulated using conventional molecular dynamics (cMD) and steered molecular dynamics (sMD) simulations of a structural model of MBNL1 protein to provide insights into the binding selectivity of the four zinc-finger (ZnF) domains toward the GpC steps in YGCY RNA sequence. In accordance with previous studies, our results suggest that both global and local residue fluctuations on each domain have great impacts on triggering alternative splicing, indicating that local motions in RNA-binding domains could modulate their affinity and specificity. In addition, all four ZnF domains provide a distinct RNA-binding environment in terms of structural sampling and mobility that may be involved in the differentiated MBNL1 splicing events reported in the literature.


Assuntos
Processamento Alternativo , Distrofia Miotônica , Humanos , Simulação de Dinâmica Molecular , RNA/genética , RNA/metabolismo , Splicing de RNA , Distrofia Miotônica/genética , Zinco/metabolismo , Proteínas de Ligação a RNA/metabolismo
20.
Genes (Basel) ; 13(12)2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-36553680

RESUMO

Metallothionein (MT) is a multifunctional inducible protein in animals, plants, and microorganisms. MT is rich in cysteine residues (10-30%), can combine with metal ions, has a low molecular weight, and plays an essential biological role in various stages of the growth and development of organisms. Due to its strong ability to bind metal ions and scavenge free radicals, metallothionein has been used in medicine, health care, and other areas. Zinc is essential for plant growth, but excessive zinc (Zn) is bound to poison plants, and cadmium (Cd) is a significant environmental pollutant. A high concentration of cadmium can significantly affect the growth and development of plants and even lead to plant death. In this study, the human metallothionein gene HsMT1L under the control of the CaMV 35S constitutive promoter was transformed into tobacco, and the tolerance and accumulation capacity of transgenic tobacco plants to Zn and Cd were explored. The results showed that the high-level expression of HsMT1L in tobacco could significantly enhance the accumulation of Zn2+ and Cd2+ in both the aboveground parts and the roots compared to wild-type tobacco plants and conferred a greater tolerance to Zn and Cd in transgenic tobacco. Subcellular localization showed that HsMT1L was localized to the nucleus and cytoplasm in the tobacco. Our study suggests that HsMT1L can be used for the phytoremediation of soil for heavy metal removal.


Assuntos
Cádmio , Metalotioneína , Plantas Geneticamente Modificadas , Zinco , Humanos , Cádmio/toxicidade , Cádmio/metabolismo , Metalotioneína/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Tabaco/genética , Tabaco/metabolismo , Zinco/metabolismo , Zinco/toxicidade
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