'Pancreatic beta-cells contain large amounts of zinc. We took advantage of this to try to localize, quantify, and isolate insulin-producing cells from islet preparations. Our study was designed to identify a non-toxic zinc-sensitive fluorescent probe able to selectively label labile zinc in viable beta-cells and to exhibit excitation and emission ... More
Fluorescence imaging study of extracellular zinc at the hippocampal mossy fiber synapse.
AuthorsBastian C, Li YV
JournalNeurosci Lett
PubMed ID17485170
'Although synaptically released, vesicular Zn(2+) has been proposed to play a neuromodulatory or neuronal signaling role at the mossy fiber-CA3 synapse, Zn(2+) release remains controversial, especially when detected using fluorescent imaging. In the present study, we investigated synaptically released Zn(2+) at the mossy fiber (MF) synapse in rat hippocampal slices ... More
Determining zinc with commonly used calcium and zinc fluorescent indicators, a question on calcium signals.
AuthorsMartin JL, Stork CJ, Li YV
JournalCell Calcium
PubMed ID16764924
'Investigations into the roles of Ca(2+) and Zn(2+) in cell biology have been facilitated by the development of sensitive fluorometric probes that have enabled the measurement of Ca(2+) or Zn(2+) in both extracellular and intracellular environments. It is critical to be aware of the specificity and relative selectivity of a ... More
Fluorescent zinc indicators for neurobiology.
AuthorsThompson RB, Peterson D, Mahoney W, Cramer M, Maliwal BP, Suh SW, Frederickson C, Fierke C, Herman P
JournalJ Neurosci Methods
PubMed ID12191759
'Mounting evidence indicates that zinc has multiple roles in cell biology, viz. as a part of metalloenzyme catalytic sites, as a structural component of gene regulatory proteins, and (like calcium) as a free signal ion, particularly in the cortex of the brain. While most Zn(II) in the brain is tightly ... More
Inactivation of HIV-1 nucleocapsid protein P7 by pyridinioalkanoyl thioesters. Characterization of reaction products and proposed mechanism of action.
AuthorsBasrur V, Song Y, Mazur SJ, Higashimoto Y, Turpin JA, Rice WG, Inman JK, Appella E
JournalJ Biol Chem
PubMed ID10809733
'The synthesis and antiviral properties of pyridinioalkanoyl thioester (PATE) compounds that target nucleocapsid p7 protein (NCp7) of the human immunodeficiency virus type 1 (HIV-1) have been described previously (Turpin, J. A., Song, Y., Inman, J. K., Huang, M., Wallqvist, A., Maynard, A., Covell, D. G., Rice, W. G., and Appella, ... More
Measuring cell viability with membrane impermeable zinc fluorescent indicator.
AuthorsStork CJ, Li YV,
JournalJ Neurosci Methods
PubMed ID16466804
'Recent findings suggest that the accumulation of cytoplasmic zinc [Zn2+]i is a ubiquitous component in the cell death cascade. Zn2+ can be liberated from intracellular stores following oxidative stress and contribute to cell death processes. Here we show that the membrane/cell impermeable Zn2+ fluorescent indicator Newport Green (NG), which is ... More
Protection by glycine against hypoxic injury of rat hepatocytes: inhibition of ion fluxes through nonspecific leaks.
AuthorsFrank A, Rauen U, de Groot H
JournalJ Hepatol
PubMed ID10673068
'BACKGROUND/AIMS: Glycine has long been shown to exert strong protective effects against hypoxic injury of hepatocytes. Recently, it was suggested that glycine exerts this protection via inhibition of ligand-gated chloride channels, thereby secondarily inhibiting sodium influx. The purpose of this study was to examine this suggestion. METHODS: Cultured rat hepatocytes ... 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
A sodium zinc exchange mechanism is mediating extrusion of zinc in mammalian cells.
AuthorsOhana E, Segal D, Palty R, Ton-That D, Moran A, Sensi SL, Weiss JH, Hershfinkel M, Sekler I
JournalJ Biol Chem
PubMed ID14581475
'Zinc influx, driven by a steep inward electrochemical gradient, plays a fundamental role in zinc signaling and in pathophysiologies linked to intracellular accumulation of toxic zinc. Yet, the cellular transport mechanisms that actively generate or maintain the transmembrane gradients are not well understood. We monitored Na+-dependent Zn2+ transport in HEK293 ... More
Binding of zinc(II) and copper(II) to the full-length Alzheimer's amyloid-beta peptide.
AuthorsTõugu V, Karafin A, Palumaa P,
JournalJ Neurochem
PubMed ID18289347
'There is evidence that binding of metal ions like Zn2+ and Cu2+ to amyloid beta-peptides (Abeta) may contribute to the pathogenesis of Alzheimer''s disease. Cu2+ and Zn2+ form complexes with Abeta peptides in vitro; however, the published metal-binding affinities of Abeta vary in an enormously large range. We studied the ... More
Measurement of intracellular free zinc concentrations accompanying zinc-induced neuronal death.
AuthorsCanzoniero LM, Turetsky DM, Choi DW
JournalJ Neurosci
PubMed ID10493776
'Toxic zinc influx may contribute to selective neuronal death after transient global ischemia. We previously used the high-affinity (K(D) = 27 nm) fluorescent dye mag-fura-5 to detect initial increases in neuronal intracellular free Zn(2+) ([Zn(2+)](i)) associated with brief Zn(2+) exposure. Here we used the specific low-affinity Zn(2+) indicator Newport Green ... More
Identification of genes responsive to intracellular zinc depletion in the human colon adenocarcinoma cell line HT-29.
AuthorsKindermann B, Döring F, Pfaffl M, Daniel H
JournalJ Nutr
PubMed ID14704293
'Zinc is essential for the structural and functional integrity of cells and plays a pivotal role in the control of gene expression. To identify genes with altered mRNA expression level after zinc depletion, we employed oligonucleotide arrays with approximately 10,000 targets and used the human colon adenocarcinoma epithelial cell line ... More
Visualization of transmitter release with zinc fluorescence detection at the mouse hippocampal mossy fibre synapse.
AuthorsQian J, Noebels JL
JournalJ Physiol
PubMed ID15919713
'Exocytosis of synaptic vesicle contents defines the quantal nature of neurotransmitter release. Here we developed a technique to directly assess exocytosis by measuring vesicular zinc release with the zinc-sensitive dye FluoZin-3 at the hippocampal mossy fibre (MF) synapse. Using a photodiode, we were able to clearly resolve the zinc fluorescence ... More
Detection of heavy metals in water by fluorescence spectroscopy: on the way to a suitable sensor system.
AuthorsPrestel H, Gahr A, Niessner R
JournalFresenius J Anal Chem
PubMed ID11220577
In order to develop a fiber optical heavy metal ion detection system, the applicability of selected complexing agents with fluorescent properties has been studied. Beginning with the application of known chelators, like BTC-5N, Newport Green, neocuproine, and chromotropic acid, a sensor configuration has been found, which allows the detection of ... More
The interaction of biological and noxious transition metals with the zinc probes FluoZin-3 and Newport Green.
AuthorsZhao J, Bertoglio BA, Devinney MJ, Dineley KE, Kay AR,
JournalAnal Biochem
PubMed ID18848515
Zinc-sensitive fluorescent probes have become increasingly important in the investigation of the cellular roles of zinc. There is, however, little information on how the other transition metals in cells may influence the measurement of zinc. We have characterized in vitro the interaction of the nominal zinc indicators FluoZin-3 and Newport ... More
Detection of zinc translocation into apical dendrite of CA1 pyramidal neuron after electrical stimulation.
AuthorsSuh SW,
JournalJ Neurosci Methods
PubMed ID18929598
Translocation of the endogenous cation zinc from presynaptic terminals to postsynaptic neurons after brain insult has been implicated as a potential neurotoxic event. Several studies have previously demonstrated that a brief electrical stimulation is sufficient to induce the translocation of zinc from presynaptic vesicles into the cytoplasm (soma) of postsynaptic ... More
Novel fluorescence assay for tracking molecular and cellular allergen-protein interactions.
AuthorsThierse HJ, Helm S, Pink M, Weltzien HU,
JournalJ Immunol Methods
PubMed ID17880993
T cells recognizing nickel (Ni) are key mediators in human Ni allergy, which represents the most common form of human contact hypersensitivity. In contrast to well-characterized Ni-specific human T cell clones, molecular knowledge about the extra- and intracellular route(s) of antigen/allergen presentation and processing of Ni-specific epitopes is still fragmentary. ... More
Pancreatic beta-cells secrete insulin in fast- and slow-release forms.
AuthorsMichael DJ, Ritzel RA, Haataja L, Chow RH,
JournalDiabetes
PubMed ID16505221
Insulin vesicles contain a chemically rich mixture of cargo that includes ions, small molecules, and proteins. At present, it is unclear if all components of this cargo escape from the vesicle at the same rate or to the same extent during exocytosis. Here, we demonstrate through real-time imaging that individual ... More
Fluorescence detection of redox-sensitive metals in neuronal culture: focus on iron and zinc.
AuthorsReynolds IJ
JournalAnn N Y Acad Sci
PubMed ID15105253
Detection of neurotoxic metals in the intracellular milieu has made an important contribution to the understanding of the mechanism of metal-induced neuronal injury. Fluorescent, metal-sensitive dyes have proven to be valuable in the measurement of a variety of neurotoxic cations in neurons, and these dyes have provided a number of ... 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
A fluorescent PEBBLE nanosensor for intracellular free zinc.
AuthorsSumner JP, Aylott JW, Monson E, Kopelman R
JournalAnalyst
PubMed ID11827375
The development and characterisation of a fluorescent optical PEBBLE (Probe Encapsulated By Biologically Localised Embedding) nanosensor for the detection of zinc is detailed. A ratiometric sensor has been fabricated that incorporates two fluorescent dyes; one is sensitive to zinc and the other acts as a reference. The sensing components are ... More
A reevaluation of neuronal zinc measurements: artifacts associated with high intracellular dye concentration.
AuthorsDineley KE, Malaiyandi LM, Reynolds IJ
JournalMol Pharmacol
PubMed ID12181438
The emergence of zinc as a potent neurotoxin has prompted the development of techniques suitable for the measurement of intracellular free zinc ([Zn(2+)](i)) in cultured cells. Accordingly, a new family of Zn(2+)-sensitive fluorophores has become available. Using ionophore-induced elevations of [Zn(2+)](i) in cultured neurons, we measured [Zn(2+)](i)-induced changes in the ... More
Induction of neuronal apoptosis by thiol oxidation: putative role of intracellular zinc release.
AuthorsAizenman E, Stout AK, Hartnett KA, Dineley KE, McLaughlin B, Reynolds IJ
JournalJ Neurochem
PubMed ID11032877
The membrane-permeant oxidizing agent 2,2'-dithiodipyridine (DTDP) can induce Zn(2+) release from metalloproteins in cell-free systems. Here, we report that brief exposure to DTDP triggers apoptotic cell death in cultured neurons, detected by the presence of both DNA laddering and asymmetric chromatin formation. Neuronal death was blocked by increased extracellular potassium ... More
Zinc permeates mouse muscle ACh receptor channels expressed in BOSC 23 cells and affects channel function.
AuthorsRagozzino D, Giovannelli A, Degasperi V, Eusebi F, Grassi F
JournalJ Physiol
PubMed ID11080253
1. The influx of Zn2+ through the channels of fetal and adult mouse muscle nicotinic acetylcholine receptors (gamma- and epsilon-AChRs) and its effects on receptor function were studied in transiently transfected human BOSC 23 cells, by combining patch-clamp recordings with digital fluorescence microscopy. 2. ACh-induced whole-cell currents were reversibly reduced ... More
AuthorsUeno S, Tsukamoto M, Hirano T, Kikuchi K, Yamada MK, Nishiyama N, Nagano T, Matsuki N, Ikegaya Y
JournalJ Cell Biol
PubMed ID12119362
Although Zn2+ is contained in large amounts in the synaptic terminals of hippocampal mossy fibers (MFs), its physiological role in synaptic transmission is poorly understood. By using the newly developed high-sensitivity Zn2+ indicator ZnAF-2, the spatiotemporal dynamics of Zn2+ was monitored in rat hippocampal slices. When high-frequency stimulation was delivered ... More
Excitation ratiometric fluorescent biosensor for zinc ion at picomolar levels.
AuthorsThompson RB, Cramer ML, Bozym R
JournalJ Biomed Opt
PubMed ID12421121
Zinc is a metal ion of increasing significance in several biomedical fields, including neuroscience, immunology, reproductive biology, and cancer. Fluorescent indicators have added greatly to our understanding of the biology of several metal ions, most notably calcium. Despite substantial efforts, only recently have zinc indicators been developed which are sufficiently ... More
Metal-protein complex-mediated transport and delivery of Ni2+ to TCR/MHC contact sites in nickel-specific human T cell activation.
AuthorsThierse HJ, Moulon C, Allespach Y, Zimmermann B, Doetze A, Kuppig S, Wild D, Herberg F, Weltzien HU
JournalJ Immunol
PubMed ID14734778
Nickel allergy clearly involves the activation of HLA-restricted, skin-homing, Ni-specific T cells by professional APCs. Nevertheless, knowledge concerning the molecular details of metal-protein interactions underlying the transport and delivery of metal ions to APC during the early sensitization phase and their interactions with HLA and TCRs is still fragmentary. This ... More
Mitochondrial sequestration and Ca(2+)-dependent release of cytosolic Zn(2+) loads in cortical neurons.
AuthorsSensi SL, Ton-That D, Weiss JH
JournalNeurobiol Dis
PubMed ID12127148
The endogenous divalent cations, Ca(2+) and Zn(2+), are both highly toxic upon excessive glutamate triggered intracellular accumulation. Given apparent parallels in their neurotoxic mechanisms, the present study aimed to explore interactions between these cations, by examining effects of moderate intracellular Zn(2+) loading on responses to subsequent Ca(2+) influx. Cortical cultures ... More
Blockade of Ca2+-permeable AMPA/kainate channels decreases oxygen-glucose deprivation-induced Zn2+ accumulation and neuronal loss in hippocampal pyramidal neurons.
AuthorsYin HZ, Sensi SL, Ogoshi F, Weiss JH
JournalJ Neurosci
PubMed ID11850455
Synaptic release of Zn2+ and its translocation into postsynaptic neurons probably contribute to neuronal injury after ischemia or epilepsy. Studies in cultured neurons have revealed that of the three major routes of divalent cation entry, NMDA channels, voltage-sensitive Ca2+ channels (VSCCs), and Ca2+-permeable AMPA/kainate (Ca-A/K) channels, Ca-A/K channels exhibit the ... More
Structure-function analysis of HKE4, a member of the new LIV-1 subfamily of zinc transporters.
AuthorsTaylor KM, Morgan HE, Johnson A, Nicholson RI
JournalBiochem J
PubMed ID14525538
The KE4 proteins are an emerging group of proteins with little known functional data. In the present study, we report the first characterization of the recombinant human KE4 protein in mammalian cells. The KE4 sequences are included in the subfamily of ZIP (Zrt-, Irt-like Proteins) zinc transporters, which we have ... 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
Identification of insulin-producing cells derived from embryonic stem cells by zinc-chelating dithizone.
AuthorsShiroi A, Yoshikawa M, Yokota H, Fukui H, Ishizaka S, Tatsumi K, Takahashi Y
JournalStem Cells
PubMed ID12110697
BACKGROUND AND AIMS: Embryonic stem (ES) cells have a pluripotent ability to differentiate into a variety of cell lineages in vitro. We have recently identified the emergence of cellular clusters within differentiated ES cell cultures by staining with dithizone (DTZ). DTZ is a zinc-chelating agent known to selectively stain pancreatic ... More
Zn2+ current is mediated by voltage-gated Ca2+ channels and enhanced by extracellular acidity in mouse cortical neurones.
1. Mammalian neuronal voltage-gated Ca2+ channels have been implicated as potential mediators of membrane permeability to Zn2+. We tested directly whether voltage-gated Ca2+ channels can flux Zn2+ in whole-cell voltage-clamp recordings from cultured murine cortical neurones. 2. In the presence of extracellular Zn2+ and no Na+, K+, or other divalent ... More