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Zinc homeostasis

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https://www.readbyqxmd.com/read/28303424/inherited-disorders-of-transition-metal-metabolism-an-update
#1
REVIEW
Peter T Clayton
Elements with a biological role include six trace transition metals: manganese, iron, cobalt, copper, zinc and molybdenum. Transition metals participate in group transfer reactions such as glycosylation and phosphorylation and those that can transfer an electron by alternating between two redox states such as iron (3+/2+) and copper (2+/1+) are also very important in biological redox reactions including the reduction of molecular oxygen and the transport of oxygen. However, these trace metals are also potentially toxic, generating reactive oxygen species through Fenton chemistry...
March 16, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28299743/computational-approaches-to-matrix-metalloprotease-drug-design
#2
Tanya Singh, B Jayaram, Olayiwola Adedotun Adekoya
Matrix metalloproteinases (MMPs) are a family of zinc-containing enzymes required for homeostasis. These enzymes are an important class of drug targets as their over expression is associated with many disease states. Most of the inhibitors reported against this class of proteins have failed in clinical trials due to lack of specificity. In order to assist in drug design endeavors for MMP targets, a computationally tractable pathway is presented, comprising, (1) docking of small molecule inhibitors against the target MMPs, (2) derivation of quantum mechanical charges on the zinc ion in the active site and the amino acids coordinating with zinc including the inhibitor molecule, (3) molecular dynamics simulations on the docked ligand-MMP complexes, and (4) evaluation of binding affinities of the ligand-MMP complexes via an accurate scoring function for zinc containing metalloprotein-ligand complexes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28294049/in-silico-analysis-of-amp-activated-protein-kinase-and-ligand-based-virtual-screening-for-identification-of-novel-ampk-activators
#3
Ammarah Ghaffar, Sidra Batool, Gohar Mushtaq, Muhammad Amjad Kamal
BACKGROUND: Adenosine-Monophosphate-Activated protein kinase (AMPK) is a conserved kinase that plays an important role in maintaining the homeostasis of cells. AMPK activation has a positive impact on treatment of diseases such as diabetes, obesity and cancer as well. This observation led to the development of AMPK activators. Certain naturally occurring compounds have also been known to activate AMPK. METHOD: In this study, we retrieved the AMPK activators that includes chemical drugs, xenobiotics and natural compounds and analyzed their interactions with AMPK via docking studies...
March 9, 2017: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/28288093/malaria-parasites-possess-a-telomere-repeat-binding-protein-that-shares-ancestry-with-transcription-factor-iiia
#4
Nicole L Bertschi, Christa G Toenhake, Angela Zou, Igor Niederwieser, Rob Henderson, Suzette Moes, Paul Jenoe, John Parkinson, Richard Bartfai, Till S Voss
Telomere repeat-binding factors (TRFs) are essential components of the molecular machinery that regulates telomere function. TRFs are widely conserved across eukaryotes and bind duplex telomere repeats via a characteristic MYB-type domain. Here, we identified the telomere repeat-binding protein PfTRZ in the malaria parasite Plasmodium falciparum, a member of the Alveolate phylum for which TRFs have not been described so far. PfTRZ lacks an MYB domain and binds telomere repeats via a C2H2-type zinc finger domain instead...
March 13, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28285974/associations-between-dietary-intakes-of-iron-copper-and-zinc-with-risk-of-type-2-diabetes-mellitus-a-large-population-based-prospective-cohort-study
#5
Ehab S Eshak, Hiroyasu Iso, Koutatsu Maruyama, Isao Muraki, Akiko Tamakoshi
BACKGROUND & AIMS: Abnormal homeostasis of iron, copper and zinc has been included in the pathogenesis of type 2 diabetes mellitus (T2DM). However, the evidence of associations between dietary intakes of these elements and T2DM is limited. We thought to examine the association between dietary intakes of iron, copper and zinc with risk of T2DM in Japanese population. METHODS: A prospective study encompassing 16,160 healthy Japanese men and women aged 40-65 years in whom the associations between dietary intakes of iron, copper and zinc, determined by a validated self-administered food frequency questionnaire, with risk of 5-year cumulative incidence of validated physician-diagnosed T2DM, were evaluated by logistic regression model...
February 28, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28281200/zntr-positively-regulates-t6ss4-expression-in-yersinia-pseudotuberculosis
#6
Tietao Wang, Keqi Chen, Fen Gao, Yiwen Kang, Muhammad Tausif Chaudhry, Zhuo Wang, Yao Wang, Xihui Shen
The type VI secretion system (T6SS) is a widespread and versatile protein secretion system found in most Gramnegative bacteria. Studies of T6SS have mainly focused on its role in virulence toward host cells and inter-bacterial interactions, but studies have also shown that T6SS4 in Yersinia pseudotuberculosis participates in the acquisition of zinc ions to alleviate the accumulation of hydroxyl radicals induced by multiple stressors. Here, by comparing the gene expression patterns of wild-type and zntR mutant Y...
March 10, 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/28268202/adverse-effects-of-parental-zinc-deficiency-on-metal-homeostasis-and-embryonic-development-in-a-zebrafish-model
#7
Laura M Beaver, Yasmeen M Nkrumah-Elie, Lisa Truong, Carrie L Barton, Andrea L Knecht, Greg D Gonnerman, Carmen P Wong, Robert L Tanguay, Emily Ho
The high prevalence of zinc deficiency is a global public health concern, and suboptimal maternal zinc consumption has been associated with adverse effects ranging from impaired glucose tolerance to low birthweights. The mechanisms that contribute to altered development and poor health in zinc deficient offspring are not completely understood. To address this gap, we utilized the Danio rerio model and investigated the impact of dietary zinc deficiency on adults and their developing progeny. Zinc deficient adult fish were significantly smaller in size, and had decreases in learning and fitness...
February 20, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28264932/zinc-starvation-induces-autophagy-in-yeast
#8
Tomoko Kawamata, Tetsuro Horie, Miou Matsunami, Michiko Sasaki, Yoshinori Ohsumi
Zinc is an essential nutrient for all forms of life. Within cells, most zinc is bound to protein. Because zinc serves as a catalytic or structural cofactor for many proteins, cells must maintain zinc homeostasis under severely zinc-deficient conditions. In yeast, the transcription factor Zap1 controls the expression of genes required for uptake and mobilization of zinc, but to date the fate of existing zinc-binding proteins under zinc starvation remains poorly understood. Autophagy is an evolutionarily conserved cellular degradation/recycling process in which cytoplasmic proteins and organelles are sequestered for degradation in the vacuole/lysosome...
March 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28258171/znf503-zpo2-drives-aggressive-breast-cancer-progression-by-down-regulation-of-gata3-expression
#9
Payam Shahi, Chih-Yang Wang, Devon A Lawson, Euan M Slorach, Angela Lu, Ying Yu, Ming-Derg Lai, Hugo Gonzalez Velozo, Zena Werb
The transcription factor GATA3 is the master regulator that drives mammary luminal epithelial cell differentiation and maintains mammary gland homeostasis. Loss of GATA3 is associated with aggressive breast cancer development. We have identified ZNF503/ZEPPO2 zinc-finger elbow-related proline domain protein 2 (ZPO2) as a transcriptional repressor of GATA3 expression and transcriptional activity that induces mammary epithelial cell proliferation and breast cancer development. We show that ZPO2 is recruited to GATA3 promoter in association with ZBTB32 (Repressor of GATA, ROG) and that ZBTB32 is essential for down-regulation of GATA3 via ZPO2...
March 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28250320/metal-mediated-epigenetic-regulation-of-gene-expression
#10
Tomoki Kimura
 Epigenetics is the study of heritable changes in gene expression that occur without alterations in the DNA sequence. Several studies have shown that environmental chemicals can alter epigenetic modifications, including histone modifications and DNA methylation. Environmental chemicals may show toxic effects via epigenetic mechanism-regulated changes in gene expression. Previously, we reported that zinc treatment rapidly decreased Lys(4)-trimethylated and Lys(9)-acetylated histone H3 in the metallothionein (MT) promoter, and also decreased total histone H3...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28248532/trace-elements-have-beneficial-as-well-as-detrimental-effects-on-bone-homeostasis
#11
I Zofkova, M Davis, J Blahos
The protective role of nutrition factors such as calcium, vitamin D and vitamin K for the integrity of the skeleton is well understood. In addition, integrity of the skeleton is positively influenced by certain trace elements (e.g. zinc, copper, manganese, magnesium, iron, selenium, boron and fluoride) and negatively by others (lead, cadmium, cobalt). Deficiency or excess of these elements influence bone mass and bone quality in adulthood as well as in childhood and adolescence. However, some protective elements may become toxic under certain conditions, depending on dosage (serum concentration), duration of treatment and interactions among individual elements...
February 28, 2017: Physiological Research
https://www.readbyqxmd.com/read/28247282/backbone-1-h-13-c-and-15-n-nmr-resonance-assignments-of-the-kr%C3%A3-ppel-like-factor-4-activation-domain
#12
Brigid S Conroy, Emma R Weiss, Steven P Smith, David N Langelaan
Krüppel-like factor 4 (KLF4) is a transcription factor involved in diverse biological processes, including development, cellular differentiation and proliferation, and maintenance of tissue homeostasis. KLF4 has also been associated with disease states, such as cardiovascular disease and several cancers. KLF4 contains an activation domain, repression domain, and a structurally characterized C-terminal zinc finger domain that mediates its binding to DNA. The structurally uncharacterized KLF4 activation domain is critical for transactivation by KLF4 and mediates its binding to the transcriptional coactivator CBP/p300...
February 28, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28215299/zinc-interactions-with-brain-derived-neurotrophic-factor-and-related-peptide-fragments
#13
A Travaglia, D La Mendola
Brain-derived neurotrophic factor (BDNF) is a neurotrophin essential for neuronal development and survival, synaptic plasticity, and cognitive function. Dysregulation of BDNF signaling is involved in several neurodegenerative disorders, including Alzheimer's disease. Alteration of metal ion homeostasis is observed both in normal aging and in many neurodegenerative diseases. Interestingly, there is a significant overlap between brain areas characterized by metal ion dyshomeostasis and those where BDNF exerts its biological activity...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28209778/role-for-dithiolopyrrolones-in-disrupting-bacterial-metal-homeostasis
#14
Andrew N Chan, Anthony L Shiver, Walter J Wever, Sayyeda Zeenat A Razvi, Matthew F Traxler, Bo Li
Natural products harbor unique and complex structures that provide valuable antibiotic scaffolds. With an increase in antibiotic resistance, natural products once again hold promise for new antimicrobial therapies, especially those with unique scaffolds that have been overlooked due to a lack of understanding of how they function. Dithiolopyrrolones (DTPs) are an underexplored class of disulfide-containing natural products, which exhibit potent antimicrobial activities against multidrug-resistant pathogens...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28199213/the-zinc-sensing-receptor-znr-gpr39-in-health-and-disease
#15
Laxmi Sunuwar, David Gilad, Michal Hershfinkel
While zinc has had a well-established structural role for many years, it is only during the last two decades that its role as a signaling molecule has been recognized. Ionic zinc, Zn(2+), that is endogenously released during physiological activity acts as a first messenger, triggering the activity of a distinct Zn(2+)-sensing-receptor, ZnR. The ZnR is a member of the Gq-coupled receptor family, and the molecular moiety mediating its activity is GPR39. In this review, we will discuss the role of the ZnR/GPR39 in mediating Zn(2+)-dependent signaling in epithelial tissues and in neurons, where Zn(2+) homeostasis plays physiological as well as pathological roles...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28199205/the-mucolipin-1-trpml1-ion-channel-transmembrane-163-tmem163-protein-and-lysosomal-zinc-handling
#16
Math P Cuajungco, Kirill Kiselyov
Lysosomes are emerging as important players in cellular zinc ion (Zn(2+)) homeostasis. The series of work on Zn2+ accumulation in the neuronal lysosomes and the mounting evidence on the role of lysosomal Zn(2+) in cell death during mammary gland involution set a biological precedent for the central role of the lysosomes in cellular Zn(2+) handling. Such a role appears to involve cytoprotection on the one hand, and cell death on the other. The recent series of work began to identify the molecular determinants of the lysosomal Zn(2+) handling...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28197076/structure-and-synaptic-function-of-metal-binding-to-the-amyloid-precursor-protein-and-its-proteolytic-fragments
#17
REVIEW
Klemens Wild, Alexander August, Claus U Pietrzik, Stefan Kins
Alzheimer's disease (AD) is ultimately linked to the amyloid precursor protein (APP). However, current research reveals an important synaptic function of APP and APP-like proteins (APLP1 and 2). In this context various neurotrophic and neuroprotective functions have been reported for the APP proteolytic fragments sAPPα, sAPPβ and the monomeric amyloid-beta peptide (Aβ). APP is a metalloprotein and binds copper and zinc ions. Synaptic activity correlates with a release of these ions into the synaptic cleft and dysregulation of their homeostasis is linked to different neurodegenerative diseases...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28196538/functional-studies-of-drosophila-zinc-transporters-reveal-the-mechanism-for-zinc-excretion-in-malpighian-tubules
#18
Sai Yin, Qiuhong Qin, Bing Zhou
BACKGROUND: Zinc is an essential metal involved in many physiological processes. Previous work has identified a set of zinc transporters involved in Drosophila dietary zinc absorption. However, zinc excretion and reabsorption, the other two important processes to maintain zinc homeostasis, are not as well understood. In this work, we screened all the potential zinc transporter Zip (SLC39) and ZnT (SLC30) members for their likely roles in zinc excretion in Malpighian tubules, an insect organ functionally analogous to mammalian kidneys...
February 14, 2017: BMC Biology
https://www.readbyqxmd.com/read/28195154/zinc-finger-protein-zpr9-functions-as-an-activator-of-ampk-related-serine-threonine-kinase-mpk38-melk-involved-in-ask1-tgf-%C3%AE-p53-signaling-pathways
#19
Hyun-A Seong, Ravi Manoharan, Hyunjung Ha
Murine protein serine-threonine kinase 38 (MPK38), an AMP-activated protein kinase (AMPK)-related kinase, has been implicated in the induction of apoptosis signal-regulating kinase 1 (ASK1)-, transforming growth factor-β (TGF-β)-, and p53-mediated activity involved in metabolic homeostasis. Here, zinc finger protein ZPR9 was found to be an activator of MPK38. The association of MPK38 and ZPR9 was mediated by cysteine residues present in each of these two proteins, Cys(269) and Cys(286) of MPK38 and Cys(305) and Cys(308) of ZPR9...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194465/unravelling-the-role-of-protein-kinase-ck2-in-metal-toxicity-using-gene-deletion-mutants
#20
Adam J Johnson, Mohammad S Zaman, Filip Veljanoski, Alex A Phrakaysone, Suhua Li, Patrick J O'Doherty, Gayani Petersingham, Gabriel G Perrone, Mark P Molloy, Ming J Wu
Metal ions, biologically essential or toxic, are present in the surrounding environment of living organisms. Understanding their uptake, homeostasis or detoxification is critical in cell biology and human health. In this study, we investigated the role of protein kinase CK2 in metal toxicity using gene deletion strains of Saccharomyces cerevisiae against a panel of six metal ions. The deletion of CKA2, the yeast orthologue of mammalian CK2α', leads to a pronounced resistant phenotype against Zn(2+) and Al(3+), whilst the deletion of CKB1 or CKB2 results in tolerance to Cr(6+) and As(3+)...
February 14, 2017: Metallomics: Integrated Biometal Science
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