Zn-regulated GTPase metalloprotein activator 1 modulates vertebrate zinc homeostasis

Weiss, Amy L.; Murdoch, Caitlin C.; Edmonds, Katherine A.; Jordan, Matthew R; Monteith, Andrew J.; Perera, Y. Randika; Nassif, Aslin M Rodríguez; Petoletti, Amber M; Beavers, William N.; Munneke, Matthew J; Drury, Sydney L.; Krystofiak, Evan; Thalluri, Kishore; Wu, Hongwei; Kruse, Angela; DiMarchi, Richard D.; Caprioli, Richard M.; Spraggins, Jeffrey M.; Chazin, Walter J.; Giedroc, D.P.; Skaar, Eric P.

doi:10.1016/j.cell.2022.04.011

Cited by 57 publications

(38 citation statements)

References 108 publications

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“…Zinc (Zn) is one of the essential trace elements. As a micronutrient, it functions as a cofactor for up to 10% of proteins in living organisms, playing a vital role in a range of biological processes in the human body ( 7 ). Zn is involved in a range of signaling pathways, e.g., Nuclear Factor Kappa B (NF-κB) signaling, and Toll-like Receptor 4 (TLR4) signaling, carrying considerable clinical implications ( 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

Maternal serum zinc level is associated with risk of preeclampsia: A systematic review and meta-analysis

Jin

Zheng

2022

Front. Public Health

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BackgroundPreeclampsia (PE) is a multi-organ syndrome that onsets in the second half of pregnancy. It is the second leading cause of maternal death globally. The homeostasis of zinc (Zn) levels is important for feto-maternal health.ObjectiveWe aimed to collect all studies available to synthesize the evidence regarding the association between maternal Zn levels and the risk of preeclampsia.MethodsA systematic review and meta-analysis was conducted via searching seven electronic databases [PubMed, Web of Science, Embase, African Journals Online (AJOL), ClinicalTrial.gov, and two Chinese databases: Wanfang and Chinese National Knowledge Infrastructure, CNKI]. Studies reporting maternal serum Zn levels in pregnant women with or without preeclampsia were included. Eligible studies were assessed through Newcastle-Ottawa Scale (NOS) and the meta-analysis was performed via RevMan and Stata. The random-effects method (REM) was used for the meta-analysis with 95% confidence interval (CI). The pooled result was assessed using standard mean difference (SMD). The heterogeneity test was carried out using I2 statistics, and the publication bias was evaluated using Begg's and Egger's test. Meta-regression and sensitivity analysis was performed via Stata software.ResultsA total of 51 studies were included in the final analysis. 6,947 participants from 23 countries were involved in our study. All studies went through the quality assessment. The pooled results showed that maternal serum Zn levels were lower in preeclamptic women than in healthy pregnant women (SMD: −1.00, 95% CI: −1.29, −0.70). Sub-group analysis revealed that geographical, economic context, and disease severity may further influence serum Zn levels and preeclampsia.LimitationsThere are significant between-study heterogeneity and publication bias among included studies.ConclusionsA lower level of maternal Zn was associated with increased risks of preeclampsia. The associations were not entirely consistent across countries and regions worldwide.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=337069, Identifier: CRD42022337069

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Section: Introductionmentioning

confidence: 99%

Maternal serum zinc level is associated with risk of preeclampsia: A systematic review and meta-analysis

Jin

Zheng

2022

Front. Public Health

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“…The latter then uses Guanosine-5'-triphosphate (GTP) hydrolysis to deliver a zinc(II) ion to a catalytic site on the target enzyme having lower (nM) affinity. 79 An interdigitated pattern of two zinc(II) ions is present in at least one SARS-CoV-2 protein, the Nsp13 helicase, and it may be speculated that the recruitment of a host metallochaperone can restore enzymatic activity under conditions of low cellular zinc(II).…”

Section: Resultsmentioning

confidence: 99%

The zinc proteome of SARS-CoV-2

2022

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Zinc is an essential element for human health. Among its many functions, zinc(II) modulates the immune response to infections and, at high concentrations or in the presence of ionophores, inhibits the replication of various RNA viruses. Structural biology studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed that zinc(II) is the most common metal ion that binds to viral proteins. However, the number of zinc(II)-binding sites identified by experimental methods is far from exhaustive, as metal ions may be lost during protein purification protocols. To better define the zinc(II)-binding proteome of coronavirus, we leveraged the wealth of deposited structural data and state-of-the-art bioinformatics methods. Through this in silico approach, 15 experimental zinc(II) sites were identified and a further 22 were predicted in Spike, open reading frame (ORF)3a/d, ORF8, and several nonstructural proteins, highlighting an essential role of zinc(II) in viral replication. Furthermore, the structural relationships between viral and eukaryotic sites (typically zinc fingers) indicate that SARS-CoV-2 can compete with human proteins for zinc(II) binding. Given the double-edged effect of zinc(II) ions, both essential and toxic to coronavirus, only the complete elucidation of the structural and regulatory zinc(II)-binding sites can guide selective antiviral strategies based on zinc supplementation.

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“…In terms of biocompatibility, Zn is the second most abundant transition metal in humans, serving as a structural or enzymatic cofactor for approximately 10% of the proteome [ 29 ]. Consequently, perturbations in Zn homeostasis may lead to various disorders, including growth deficiencies, immune defects, neurological disorders, and cancers [ 30 ]. Studies also found that Zn ions (Zn 2+ ) play an important role in promoting fracture healing [ 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, perturbations in Zn homeostasis may lead to various disorders, including growth deficiencies, immune defects, neurological disorders, and cancers [ 30 ]. Studies also found that Zn ions (Zn 2+ ) play an important role in promoting fracture healing [ 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

Zinc-Based Biodegradable Materials for Orthopaedic Internal Fixation

Liu

Qiao

et al. 2022

JFB

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Traditional inert materials used in internal fixation have caused many complications and generally require removal with secondary surgeries. Biodegradable materials, such as magnesium (Mg)-, iron (Fe)- and zinc (Zn)-based alloys, open up a new pathway to address those issues. During the last decades, Mg-based alloys have attracted much attention by researchers. However, the issues with an over-fast degradation rate and release of hydrogen still need to be overcome. Zn alloys have comparable mechanical properties with traditional metal materials, e.g., titanium (Ti), and have a moderate degradation rate, potentially serving as a good candidate for internal fixation materials, especially at load-bearing sites of the skeleton. Emerging Zn-based alloys and composites have been developed in recent years and in vitro and in vivo studies have been performed to explore their biodegradability, mechanical property, and biocompatibility in order to move towards the ultimate goal of clinical application in fracture fixation. This article seeks to offer a review of related research progress on Zn-based biodegradable materials, which may provide a useful reference for future studies on Zn-based biodegradable materials targeting applications in orthopedic internal fixation.

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Zn-regulated GTPase metalloprotein activator 1 modulates vertebrate zinc homeostasis

Cited by 57 publications

References 108 publications

Maternal serum zinc level is associated with risk of preeclampsia: A systematic review and meta-analysis

Maternal serum zinc level is associated with risk of preeclampsia: A systematic review and meta-analysis

The zinc proteome of SARS-CoV-2

Zinc-Based Biodegradable Materials for Orthopaedic Internal Fixation

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