Calcineurin/nuclear factor of activated T cells and MAPK signaling induce TNF-{alpha} gene expression in pancreatic islet endocrine cells.
AuthorsLawrence MC, Naziruddin B, Levy MF, Jackson A, McGlynn K,
JournalJ Biol Chem
PubMed ID21059644
Cytokines contribute to pancreatic islet inflammation, leading to impaired glucose homeostasis and diabetic diseases. A plethora of data shows that proinflammatory cytokines are produced in pancreatic islets by infiltrating mononuclear immune cells. Here, we show that pancreatic islet a cells and ß cells express tumor necrosis factor-a (TNF-a) and other ... More
Identification and purification of functional human beta-cells by a new specific zinc-fluorescent probe.
'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
'Synaptically released Zn2+ can enter and cause injury to postsynaptic neurons. Microfluorimetric studies using the Zn2+-sensitive probe, Newport green, examined levels of [Zn2+]i attained in cultured cortical neurons on exposure to N-methyl-D-asparte, kainate, or high K+ (to activate voltage-sensitive Ca2+ channels) in the presence of 300 microM Zn2+. Indicating particularly ... More
Measurement of intracellular free zinc in living cortical neurons: routes of entry.
'We used the ratioable fluorescent dye mag-fura-5 to measure intracellular free Zn2+ ([Zn2+]i) in cultured neocortical neurons exposed to neurotoxic concentrations of Zn2+ in concert with depolarization or glutamate receptor activation and identified four routes of Zn2+ entry. Neurons exposed to extracellular Zn2+ plus high K+ responded with a peak ... 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
Zinc is a novel intracellular second messenger.
AuthorsYamasaki S, Sakata-Sogawa K, Hasegawa A, Suzuki T, Kabu K, Sato E, Kurosaki T, Yamashita S, Tokunaga M, Nishida K, Hirano T
JournalJ Cell Biol
PubMed ID17502426
'Zinc is an essential trace element required for enzymatic activity and for maintaining the conformation of many transcription factors; thus, zinc homeostasis is tightly regulated. Although zinc affects several signaling molecules and may act as a neurotransmitter, it remains unknown whether zinc acts as an intracellular second messenger capable of ... 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
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
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
Zinc oxide nanoparticles interfere with zinc ion homeostasis to cause cytotoxicity.
AuthorsKao YY, Chen YC, Cheng TJ, Chiung YM, Liu PS,
JournalToxicol Sci
PubMed ID22112499
'The toxicological effects of zinc oxide nanoparticles (ZnO-NPs) are attracting increasing concern as the field of nanotechnology progresses. Although the literature suggests that toxicity of ZnO-NPs may be related to their dissolution, the mechanism for ZnO-NP perturbation of cytosolic zinc concentration ([Zn(2+)](c)) homeostasis remains obscure. Using FluoZin-3 and RhodZin-3, this ... More
Transient Influx of nickel in root mitochondria modulates organic acid and reactive oxygen species production in nickel hyperaccumulator Alyssum murale.
AuthorsAgrawal B, Czymmek KJ, Sparks DL, Bais HP,
JournalJ Biol Chem
PubMed ID23322782
'Mitochondria are important targets of metal toxicity and are also vital for maintaining metal homeostasis. Here, we examined the potential role of mitochondria in homeostasis of nickel in the roots of nickel hyperaccumulator plant Alyssum murale. We evaluated the biochemical basis of nickel tolerance by comparing the role of mitochondria ... More
Measurement of intracellular free zinc in living neurons.
AuthorsCanzoniero LM, Sensi SL, Choi DW
JournalNeurobiol Dis
PubMed ID9361304
Excessive Zn2+ influx has been implicated in the pathogenesis of neuronal death after global ischemia or prolonged seizures, but little is presently known about cellular regulation of intracellular free Zn2+ ([Zn2+]i). In large part, this is because the tools currently available for measuring [Zn2+]i are limited in comparison to those ... 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
Activation of the Trk signaling pathway by extracellular zinc. Role of metalloproteinases.
AuthorsHwang JJ, Park MH, Choi SY, Koh JY
JournalJ Biol Chem
PubMed ID15659400
In certain brain regions, extracellular zinc concentrations can rise precipitously as intense neuronal activity releases large amounts of zinc from the nerve terminals. Although zinc release has been suggested to play a pathological role, its precise physiological effect is poorly understood. Here, we report that exposure to micromolar quantities of ... More
Do 'passive' medical titanium surfaces deteriorate in service in the absence of wear?
AuthorsAddison O, Davenport AJ, Newport RJ, Kalra S, Monir M, Mosselmans JF, Proops D, Martin RA,
JournalJ R Soc Interface
PubMed ID22832360
Globally, more than 1000 tonnes of titanium (Ti) is implanted into patients in the form of biomedical devices on an annual basis. Ti is perceived to be 'biocompatible' owing to the presence of a robust passive oxide film (approx. 4 nm thick) at the metal surface. However, surface deterioration can ... More
Bioavailability, intracellular mobilization of nickel, and HIF-1a activation in human lung epithelial cells exposed to metallic nickel and nickel oxide nanoparticles.
AuthorsPietruska JR, Liu X, Smith A, McNeil K, Weston P, Zhitkovich A, Hurt R, Kane AB,
JournalToxicol Sci
PubMed ID21828359
Micron-sized particles of poorly soluble nickel compounds, but not metallic nickel, are established human and rodent carcinogens. In contrast, little is known about the toxic effects of a growing number of Ni-containing materials in the nano-sized range. Here, we performed physicochemical characterization of NiO and metallic Ni nanoparticles and examined ... More
Ethanol reduces zincosome formation in cultured astrocytes.
Zinc is an ion that participates in basic cellular and tissular functions. Zinc deficiency is present in many physiological and health problems affecting most body organs, including the brain. Among the circumstances involved in zinc deficiency, ethanol consumption is probably one of the most frequent. A dietary zinc supplement has ... More
Uptake and intracellular distribution of various metal ions in human monocyte-derived dendritic cells detected by Newport Green DCF diacetate ester.
BACKGROUND: The attempt to visualise intracellular protein metal complexes has currently been difficult due to the unavailability of probes for such molecular structures. Newport Green DCF diacetate ester is a cell permeant acetate ester, which becomes fluorescent after hydrolysis. This molecule is initially uncharged, allowing it to pass through cell ... 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
Chromatin-remodeling factors allow differentiation of bone marrow cells into insulin-producing cells.
AuthorsTayaramma T, Ma B, Rohde M, Mayer H,
JournalStem Cells
PubMed ID16990588
Type 1 diabetes is caused by the destruction of pancreatic beta-cells by T cells of the immune system. Islet transplantation is a promising therapy for diabetes mellitus. Bone marrow stem cells (BMSC) have the capacity to differentiate into various cell lineages including endocrine cells of the pancreas. To investigate the ... More
Oral nickel tolerance: Fas ligand-expressing invariant NK T cells promote tolerance induction by eliciting apoptotic death of antigen-carrying, effete B cells.
AuthorsNowak M, Kopp F, Roelofs-Haarhuis K, Wu X, Gleichmann E,
JournalJ Immunol
PubMed ID16585548
Whereas oral nickel administration to C57BL/6 mice (Ni(high) mice) renders the animals tolerant to immunization with NiCl2 combined with H2O2 as adjuvant, as determined by ear-swelling assay, it fails to tolerize Jalpha18-/- mice, which lack invariant NKT (iNKT) cells. Our previous work also showed that Ni(high) splenic B cells can ... 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
A human beta-cell line for transplantation therapy to control type 1 diabetes.
AuthorsNarushima M, Kobayashi N, Okitsu T, Tanaka Y, Li SA, Chen Y, Miki A, Tanaka K, Nakaji S, Takei K, Gutierrez AS, Rivas-Carrillo JD, Navarro-Alvarez N, Jun HS, Westerman KA, Noguchi H, Lakey JR, Leboulch P, Tanaka N, Yoon JW
JournalNat Biotechnol
PubMed ID16186810
A human pancreatic beta-cell line that is functionally equivalent to primary beta-cells has not been available. We established a reversibly immortalized human beta-cell clone (NAKT-15) by transfection of primary human beta-cells with a retroviral vector containing simian virus 40 large T-antigen (SV40T) and human telomerase reverse transcriptase (hTERT) cDNAs flanked ... More
Zn(2+): a novel ionic mediator of neural injury in brain disease.
AuthorsWeiss JH, Sensi SL, Koh JY
JournalTrends Pharmacol Sci
PubMed ID11050320
Zn(2+) is the second most prevalent trace element in the body and is present in particularly large concentrations in the mammalian brain. Although Zn(2+) is a cofactor for many enzymes in all tissues, a unique feature of brain Zn(2+) is its vesicular localization in presynaptic terminals, where its release is ... 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
AMPA/kainate receptor-triggered Zn2+ entry into cortical neurons induces mitochondrial Zn2+ uptake and persistent mitochondrial dysfunction.
AuthorsSensi SL, Yin HZ, Weiss JH
JournalEur J Neurosci
PubMed ID11029652
Rapid Zn2+ influx through Ca2+-permeable AMPA/kainate (Ca-A/K) channels triggers reactive oxygen species (ROS) generation and is potently neurotoxic. The first aim of this study was to determine whether these effects might result from direct mitochondrial Zn2+ uptake. Adapting the mitochondrially sequestered divalent cation sensitive probe, rhod-2, to visualize mitochondrial Zn2+, ... 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
Ca2+-dependent cytotoxicity of H2O2 in L929 cells: the role of H2O2-induced Na+-influx.
AuthorsJussofie A, Kirsch M, de Groot H
JournalFree Radic Biol Med
PubMed ID9801072
We investigated the mechanism by which H2O2 mediates an increase in [Na+]i in L929 cells and the relevance of this Na+ load for H2O2-induced cell injury. [Na+]i increased early after exposure to H2O2 as monitored by fluorescence spectrophotometry of cells loaded with SBFI. The omission of Na+ from the incubation ... 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
L-Type Calcium Channel-Mediated Zinc Wave Is Involved in the Regulation of IL-6 by Stimulating Non-IgE with LPS and IL-33 in Mast Cells and Dendritic Cells.
Authors
JournalBiol Pharm Bull
PubMed ID30416166
NO-released zinc supports the simultaneous binding of Raf-1 and PKCγ cysteine-rich domains to HINT1 protein at the mu-opioid receptor.
Authors
JournalAntioxid Redox Signal
PubMed ID21235400
Zinc reduces hepatic lipid deposition and activates lipophagy via Zn2+/MTF-1/PPARα and Ca2+/CaMKKβ/AMPK pathways.
Authors
JournalFASEB J
PubMed ID29912588
Rising intracellular zinc by membrane depolarization and glucose in insulin-secreting clonal HIT-T15 beta cells.
Authors
JournalExp Diabetes Res
PubMed ID22536213
Nitric oxide synthase activation and oxidative stress, but not intracellular zinc dyshomeostasis, regulate ultraviolet B light-induced apoptosis.
Authors
JournalLife Sci
PubMed ID20149802
Metformin alleviates nickel-induced autophagy and apoptosis via inhibition of hexokinase-2, activating lipocalin-2, in human bronchial epithelial cells.
Authors
JournalOncotarget
PubMed ID29285270
HINT1 protein cooperates with cannabinoid 1 receptor to negatively regulate glutamate NMDA receptor activity.
Authors
JournalMol Brain
PubMed ID24093505
Cannabinoid receptors couple to NMDA receptors to reduce the production of NO and the mobilization of zinc induced by glutamate.
Authors
JournalAntioxid Redox Signal
PubMed ID23600761
Autophagy Involves in Differentiation of Insulin-Secreting Cells from Adipose Derived Stem Cells.