Demand for Zn2+ in acid-secreting gastric mucosa and its requirement for intracellular Ca2+.
AuthorsLiu J, Kohler JE, Blass AL, Moncaster JA, Mocofanescu A, Marcus MA, Blakely EA, Bjornstad KA, Amarasiriwardena C, Casey N, Goldstein LE, Soybel DI,
JournalPLoS One
PubMed ID21698273
'Recent work has suggested that Zn(2+) plays a critical role in regulating acidity within the secretory compartments of isolated gastric glands. Here, we investigate the content, distribution and demand for Zn(2+) in gastric mucosa under baseline conditions and its regulation during secretory stimulation. Content and distribution of zinc were evaluated ... More
The amyloid precursor protein (APP) of Alzheimer disease and its paralog, APLP2, modulate the Cu/Zn-Nitric Oxide-catalyzed degradation of glypican-1 heparan sulfate in vivo.
AuthorsCappai R, Cheng F, Ciccotosto GD, Needham BE, Masters CL, Multhaup G, Fransson LA, Mani K
JournalJ Biol Chem
PubMed ID15677459
'Processing of the recycling proteoglycan glypican-1 involves the release of its heparan sulfate chains by copper ion- and nitric oxide-catalyzed ascorbate-triggered autodegradation. The Alzheimer disease amyloid precursor protein (APP) and its paralogue, the amyloid precursor-like protein 2 (APLP2), contain copper ion-, zinc ion-, and heparan sulfate-binding domains. We have investigated ... More
Clioquinol and pyrithione activate TRPA1 by increasing intracellular Zn2+.
AuthorsAndersson DA, Gentry C, Moss S, Bevan S,
JournalProc Natl Acad Sci U S A
PubMed ID19416844
'The antifungal and amoebicidal drug clioquinol (CQ) was withdrawn from the market when it was linked to an epidemic of subacute myelo-optico-neuropathy (SMON). Clioquinol exerts its anti-parasitic actions by acting as a Cu/Zn chelator and ionophore. Here we show that local injections of CQ produce mechanical hyperalgesia and cold hypersensitivity ... More
Intracellular zinc fluctuations modulate protein tyrosine phosphatase activity in insulin/insulin-like growth factor-1 signaling.
AuthorsHaase H, Maret W
JournalExp Cell Res
PubMed ID14644152
'Zinc is an effector of insulin/IGF-1 signaling and has insulinomimetic effects, the molecular basis of which is not understood. The present study establishes the capacity of zinc to inhibit protein tyrosine phosphatases (PTPs) as a cause for these effects and, moreover, demonstrates modulation of the insulin response by changes in ... More
Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response.
'Infection and inflammation produce systemic responses that include hypozincemia and hypoferremia. The latter involves regulation of the iron transporter ferroportin 1 by hepcidin. The mechanism of reduced plasma zinc is not known. Transcripts of the two zinc transporter gene families (ZnT and Zip) were screened for regulation in mouse liver ... More
Metals in neurobiology: probing their chemistry and biology with molecular imaging.
AuthorsQue EL, Domaille DW, Chang CJ,
JournalChem Rev
PubMed ID18426241
'In this review, we will provide a brief overview of the field of transition metals in neurobiology, focusing on the contributions of d-block metals zinc, iron, and copper to neurophysiology, aging, and neuropathology, as well as progress in the development of molecular probes for visualizing zinc, iron, and copper ion ... More
Involvement of glycosylphosphatidylinositol-linked ceruloplasmin in the copper/zinc-nitric oxide-dependent degradation of glypican-1 heparan sulfate in rat C6 glioma cells.
AuthorsMani K, Cheng F, Havsmark B, David S, Fransson LA
JournalJ Biol Chem
PubMed ID14707133
'The core protein of glypican-1, a glycosylphosphatidylinositol-linked heparan sulfate proteoglycan, can bind Cu(II) or Zn(II) ions and undergo S-nitrosylation in the presence of nitric oxide. Cu(II)-to-Cu(I)-reduction supports extensive and permanent nitrosothiol formation, whereas Zn(II) ions appear to support a more limited, possibly transient one. Ascorbate induces release of nitric oxide, ... More
Synergistic increase in cell lethality by dieldrin and H2O2 in rat thymocytes: Effect of dieldrin on the cells exposed to oxidative stress.
AuthorsChimeddorj T, Suzuki T, Murakane K, Inai M, Satoh M, Oyama Y,
Journal
PubMed ID23726008
'Dieldrin, one of persistent pesticides, is highly resistant to biotic and abiotic degradation. It is accumulated in organisms. Recent studies suggest that dieldrin exerts a potent cytotoxic action on cells exposed to oxidative stress. In this study, the effect of dieldrin on rat thymocytes exposed to hydrogen peroxide (H2O2)-induced oxidative ... More
Cell death and proliferation in acute slices and organotypic cultures of mammalian CNS.
AuthorsLossi L, Alasia S, Salio C, Merighi A,
JournalProg Neurobiol
PubMed ID19552996
'Analysis of the interplay between cell proliferation and death has been greatly advantaged by the development of CNS slice preparations. In slices, interactions between neurons and neurons and the glial cells are fundamentally preserved in a fashion close to the in vivo situation. In parallel, these preparations offer the possibility ... More
Motexafin gadolinium disrupts zinc metabolism in human cancer cell lines.
AuthorsMagda D, Lecane P, Miller RA, Lepp C, Miles D, Mesfin M, Biaglow JE, Ho VV, Chawannakul D, Nagpal S, Karaman MW, Hacia JG
JournalCancer Res
PubMed ID15867382
'To gain a better understanding of the mechanism of action of the metal cation-containing chemotherapeutic drug motexafin gadolinium (MGd), gene expression profiling analyses were conducted on plateau phase human lung cancer (A549) cell cultures treated with MGd. Drug treatment elicited a highly specific response that manifested in elevated levels of ... More
Simultaneous detection of intracellular free calcium and zinc using fura-2FF and FluoZin-3.
AuthorsDevinney MJ, Reynolds IJ, Dineley KE
JournalCell Calcium
PubMed ID15670869
'Elevation of intracellular free zinc ([Zn2+]i) probably contributes to cell death in injury paradigms involving calcium deregulation and oxidative stress such as glutamate excitotoxicity. However, it is difficult to monitor both ions simultaneously in live cells. Here we present a new method using fluorescence microscopy and the ion sensitive indicators ... More
Application of Zinpyr-1 for the investigation of zinc signals in Escherichia coli.
AuthorsHaase H, Hebel S, Engelhardt G, Rink L,
JournalBiometals
PubMed ID23324851
'Changes of the pico- to nanomolar concentration of free intracellular Zn(2+) are part of the signal transduction in mammalian cells. These zinc signals regulate the enzymatic activity of target proteins such as protein tyrosine phosphatases. For Escherichia coli, previous studies have reported diverging concentrations from femto- to picomolar, raising the ... More
Intracellular Ca(2+) and Zn(2+) signals during monochloramine-induced oxidative stress in isolated rat colon crypts.
AuthorsCima RR, Dubach JM, Wieland AM, Walsh BM, Soybel DI
JournalAm J Physiol Gastrointest Liver Physiol
PubMed ID16002562
'During acute exacerbations of inflammatory bowel diseases, oxidants are generated through the interactions of bacteria in the lumen, activated granulocytes, and cells of the colon mucosa. In this study we explored the ability of one such class of oxidants, represented by monochloramine (NH(2)Cl), to serve as agonists of Ca(2+) and ... More
Detection and imaging of zinc secretion from pancreatic beta-cells using a new fluorescent zinc indicator.
AuthorsGee KR, Zhou ZL, Qian WJ, Kennedy R
JournalJ Am Chem Soc
PubMed ID11817952
The thiol-modifying agent N-ethylmaleimide elevates the cytosolic concentration of free Zn(2+) but not of Ca(2+) in murine cortical neurons.
AuthorsGibon J, Tu P, Frazzini V, Sensi SL, Bouron A,
JournalCell Calcium
PubMed ID20667413
The membrane permeant alkylating agent N-ethylmaleimide (NEM) regulates numerous biological processes by reacting with thiol groups. Among other actions, NEM influences the cytosolic concentration of free Ca(2+) ([Ca(2+)]i). Depending on the cell type and the concentration used, NEM can promote the release of Ca(2+), affect its extrusion, stimulate or block ... More
The zinc indicator FluoZin-3 is not perturbed significantly by physiological levels of calcium or magnesium.
AuthorsZhao J, Bertoglio BA, Gee KR, Kay AR,
JournalCell Calcium
PubMed ID18353435
There has been some dispute in the literature as to the sensitivity of the zinc indicator FluoZin-3 to calcium, with suggestions that physiological levels of calcium and magnesium effectively occlude the response of the probe to zinc. In this communication we demonstrate that calcium concentrations as high as 10mM do ... More
Synthetic fluorescent sensors for studying the cell biology of metals.
AuthorsDomaille DW, Que EL, Chang CJ,
JournalNat Chem Biol
PubMed ID18277978
Metals are essential for sustaining all forms of life, but alterations in their cellular homeostasis are connected to severe human disorders, including cancer, diabetes and neurodegenerative diseases. Fluorescent small molecules that respond to metal ions in the cell with appropriate selectivity and sensitivity offer the ability to probe physiological and ... More
Functional consequences of the over-expression of TRPC6 channels in HEK cells: impact on the homeostasis of zinc.
AuthorsChevallet M, Jarvis L, Harel A, Luche S, Degot S, Chapuis V, Boulay G, Rabilloud T, Bouron A,
Journal
PubMed ID24733507
The canonical transient receptor potential 6 (TRPC6) protein is a non-selective cation channel able to transport essential trace elements like iron (Fe) and zinc (Zn) through the plasma membrane. Its over-expression in HEK-293 cells causes an intracellular accumulation of Zn, indicating that it could be involved in Zn transport. This ... More
Zinc protoporphyrin suppresses cancer cell viability through a heme oxygenase-1-independent mechanism: the involvement of the Wnt/ß-catenin signaling pathway.
AuthorsWang S, Avery JE, Hannafon BN, Lind SE, Ding WQ,
JournalBiochem Pharmacol
PubMed ID23523860
Zinc protoporphyrin (ZnPP), a known inhibitor of heme oxygenase-1 (HO-1), has been reported to have anticancer activity in both in vitro and in vivo model systems. While the mechanisms of ZnPP's anticancer activity remain to be elucidated, it is generally believed that ZnPP suppresses tumor growth through inhibition of HO-1 ... More
Oocyte-cumulus cell interactions regulate free intracellular zinc in mouse oocytes.
AuthorsLisle RS, Anthony K, Randall MA, Diaz FJ,
JournalReproduction
PubMed ID23404848
Zinc increases in the oocyte during maturation and is required for progression and completion of meiosis. The objective of this study was to determine whether cumulus cells regulate the levels of free intracellular zinc in the oocyte during maturation. In the cumulus-oocyte complex (COC) the relative level of free intracellular ... More
Zinc signals in neutrophil granulocytes are required for the formation of neutrophil extracellular traps.
AuthorsHasan R, Rink L, Haase H,
JournalInnate Immun
PubMed ID23008348
Zinc signals, i.e. changes in the free intracellular Zn(2+)concentration, are an integral component of signal transduction in several immune cells. The aim of the present study was to investigate if this is also the case in neutrophil granulocytes. One neutrophil function is NETosis, the release of a matrix composed of ... More
Intracellular free zinc during cardiac excitation-contraction cycle: calcium and redox dependencies.
AuthorsTuncay E, Bilginoglu A, Sozmen NN, Zeydanli EN, Ugur M, Vassort G, Turan B,
JournalCardiovasc Res
PubMed ID21062918
Zinc exists in biological systems as bound and histochemically reactive free Zn(2+). It is an essential structural constituent of many proteins, including enzymes from cellular signalling pathways, in which it functions as a signalling molecule. In cardiomyocytes at rest, Zn(2+) concentration is in the nanomolar range. Very little is known ... More
Zinc dyshomeostasis is linked with the loss of mucolipidosis IV-associated TRPML1 ion channel.
AuthorsEichelsdoerfer JL, Evans JA, Slaugenhaupt SA, Cuajungco MP,
JournalJ Biol Chem
PubMed ID20864526
Chelatable zinc is important in brain function, and its homeostasis is maintained to prevent cytotoxic overload. However, certain pathologic events result in intracellular zinc accumulation in lysosomes and mitochondria. Abnormal lysosomes and mitochondria are common features of the human lysosomal storage disorder known as mucolipidosis IV (MLIV). MLIV is caused ... More
Tracing of labile zinc in live fish hepatocytes using FluoZin-3.
Intracellular zinc levels are homeostatically regulated and although most is bound, a pool of labile Zn(II) is present in cells. We show here that the zinc probe FluoZin-3 is useful to monitor zinc fluxes during fluorescent imaging of the trout hepatic cell line D11. Nuclei and bulk cytosol appeared to ... More
Antiviral activity of the zinc ionophores pyrithione and hinokitiol against picornavirus infections.
AuthorsKrenn BM, Gaudernak E, Holzer B, Lanke K, Van Kuppeveld FJ, Seipelt J,
JournalJ Virol
PubMed ID18922875
We have discovered two metal ion binding compounds, pyrithione (PT) and hinokitiol (HK), that efficiently inhibit human rhinovirus, coxsackievirus, and mengovirus multiplication. Early stages of virus infection are unaffected by these compounds. However, the cleavage of the cellular eukaryotic translation initiation factor eIF4GI by the rhinoviral 2A protease was abolished ... More
Zinc and 4-hydroxy-2-nonenal mediate lysosomal membrane permeabilization induced by H2O2 in cultured hippocampal neurons.
AuthorsHwang JJ, Lee SJ, Kim TY, Cho JH, Koh JY,
JournalJ Neurosci
PubMed ID18354014
Lysosomal membrane permeabilization (LMP) is implicated in cancer cell death. However, its role and mechanism of action in neuronal death remain to be established. In the present study, we investigate the function of cellular zinc in oxidative stress-induced LMP using hippocampal neurons. Live-cell confocal microscopy with FluoZin-3 fluorescence showed that ... More
Detecting and minimizing zinc contamination in physiological solutions.
AuthorsKay AR
JournalBMC Physiol
PubMed ID15113426
BACKGROUND: To explore the role of zinc (Zn) in cellular physiology it is important to be able to control and quantify the level of Zn contamination in experimental solutions. A technique that relies on a Zn-sensitive fluorimetric probe is introduced for measuring Zn concentrations as low as 100 pM. The ... More
Regulation of two insulin granule populations within the reserve pool by distinct calcium sources.
AuthorsHao M, Li X, Rizzo MA, Rocheleau JV, Dawant BM, Piston DW
JournalJ Cell Sci
PubMed ID16317050
Insulin granule trafficking is a key step of glucose-stimulated insulin secretion from pancreatic beta cells. Using quantitative live cell imaging, we examined insulin granule movements within the reserve pool upon secretory stimulation in betaTC3 cells. For this study, we developed a custom image analysis program that permitted automatic tracking of ... More
Flow cytometric measurement of labile zinc in peripheral blood mononuclear cells.
AuthorsHaase H, Hebel S, Engelhardt G, Rink L
JournalAnal Biochem
PubMed ID16545333
Labile (i.e., free or loosely bound) zinc has the potential to modulate cellular function. Therefore, a flow cytometric assay for the measurement of labile zinc was developed to facilitate the investigation of the physiological roles of zinc. The zinc-sensitive fluorescent probe FluoZin-3 was used to quantify the amount of labile ... More
Apoptin induces tumor-specific apoptosis as a globular multimer.
The chicken anemia virus-derived Apoptin protein induces tumor-specific apoptosis. Here, we show that recombinant Apoptin protein spontaneously forms non-covalent globular aggregates comprising 30 to 40 subunits in vitro. This multimerization is robust and virtually irreversible, and the globular aggregates are also stable in cell extracts, suggesting that they remain intact ... More
Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines.
AuthorsLecane PS, Karaman MW, Sirisawad M, Naumovski L, Miller RA, Hacia JG, Magda D
JournalCancer Res
PubMed ID16357179
There is an emerging appreciation of the importance of zinc in regulating cancer cell growth and proliferation. Recently, we showed that the anticancer agent motexafin gadolinium (MGd) disrupted zinc metabolism in A549 lung cancer cells, leading, in the presence of exogenous zinc, to cell death. Here, we report the effect ... More
Zinc-buffering capacity of a eukaryotic cell at physiological pZn.
AuthorsKrezel A, Maret W
JournalJ Biol Inorg Chem
PubMed ID16924557
In spite of the paramount importance of zinc in biology, dynamic aspects of cellular zinc metabolism remain poorly defined at the molecular level. Investigations with human colon cancer (HT-29) cells establish a total cellular zinc concentration of 264 microM. Remarkably, about 10% of the potential high-affinity zinc-binding sites are not ... More
Modulation of mitochondrial function by endogenous Zn2+ pools.
Recent evidence suggests that intracellular Zn(2+) accumulation contributes to the neuronal injury that occurs in epilepsy or ischemia in certain brain regions, including hippocampus, amygdala, and cortex. Although most attention has been given to the vesicular Zn(2+) that is released into the synaptic space and may gain entry to postsynaptic ... More
ZIGIR, a Granule-Specific Zn2+ Indicator, Reveals Human Islet α Cell Heterogeneity.
Authors
JournalCell Rep
PubMed ID32668245
Slc39a5-mediated zinc homeostasis plays an essential role in venous angiogenesis in zebrafish.
Authors
JournalOpen Biol
PubMed ID33081634
Primary cilia control glucose homeostasis via islet paracrine interactions.
Authors
JournalProc Natl Acad Sci U S A
PubMed ID32253320
Pan-retroviral Nucleocapsid-Mediated Phase Separation Regulates Genomic RNA Positioning and Trafficking.
Authors
JournalCell Rep
PubMed ID32320662
Lysosomal Zn2+ release triggers rapid, mitochondria-mediated, non-apoptotic cell death in metastatic melanoma.
Authors
JournalCell Rep
PubMed ID34686351
Chelation of hippocampal zinc enhances long-term potentiation and synaptic tagging/capture in CA1 pyramidal neurons of aged rats: implications to aging and memory.
Authors
JournalAging Cell
PubMed ID27633878
Lysosome-related organelles in intestinal cells are a zinc storage site in C. elegans.
Authors
JournalCell Metab
PubMed ID22225878
Zinc ion flux during mammalian sperm capacitation.
Authors
JournalNat Commun
PubMed ID29802294
MCOLN1/TRPML1 finely controls oncogenic autophagy in cancer by mediating zinc influx.
Authors
JournalAutophagy
PubMed ID33890549
Glycan-Independent Gamete Recognition Triggers Egg Zinc Sparks and ZP2 Cleavage to Prevent Polyspermy.