Methylmercury induces activation of Notch signaling.

Abstract:

:Methylmercury (MeHg) toxicity in humans manifests deficits in neurological function. Cases of prenatal exposure to mercury have established that the developing nervous system is most highly susceptible to perturbation by MeHg. At a cellular level, MeHg-induced defects result from altered neuronal proliferation, migration and pathfinding. However, the molecular targets of MeHg that give rise to these outcomes are not fully understood. In an overall effort to identify the fundamental molecular targets of MeHg in neural development, we have explored the effects of MeHg on cell surface receptor function using the simplified Drosophila model. In this study, we investigated the potential role of MeHg to alter activity of the Notch receptor pathway, a highly conserved cell-cell signaling mechanism that controls cell fate decisions, proliferation, migration and neurite outgrowth in neural development. Notch receptor activation requires proteolysis by a cell surface ADAM metalloprotease. ADAM proteases are required for normal neural development and are activated by organomercurials, thus presenting a possible mechanism for MeHg neurotoxicity. Here, we demonstrate a concentration- and time-dependent increase in Notch receptor activity with MeHg exposure in three distinct Drosophila cell lines. Ten micromolar MeHg results in a 4-5.5-fold increase in Notch signaling as measured by the upregulation of two enhancer of split (E(spl)) target genes. MeHg-induced Notch activity also correlates with receptor proteolysis. Targeted knockdown of Notch protein expression demonstrates that MeHg induced E(spl) activation specifically requires the Notch receptor. Furthermore, MeHg-induced Notch activity is partially attenuated by the metalloprotease inhibitor, GM6001, consistent with a model in which MeHg promotes activation of ADAM metalloproteases. Finally, we demonstrate that inorganic HgCl(2) is significantly less active in inducing Notch activity, suggesting a mechanism specific to organic species of mercury. Overall, these data identify Notch as a potential target for MeHg toxicity in the developing nervous system.

journal_name

Neurotoxicology

journal_title

Neurotoxicology

authors

Bland C,Rand MD

doi

10.1016/j.neuro.2006.04.005

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

982-91

issue

6

eissn

0161-813X

issn

1872-9711

pii

S0161-813X(06)00102-1

journal_volume

27

pub_type

杂志文章
  • Brain and blood levels of bismuth after oral or parenteral administration of tripotassium-dicitrato bismuthate to rats.

    abstract::Bismuth levels in blood and brain of rats have been measured following acute or subchronic administration of tri-potassium-dicitrato bismuthate (TDB) by intraperitoneal injection or by gavage. After parenteral administration, the presence of bismuth in blood was associated with appreciable bismuth concentrations in br...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:

    authors: Abbracchio MP,Balduini W,Cavallaro A,Adamoli P,Fittipaldi M,Muzio F,Malandrino S,Cattabeni F

    更新日期:1985-10-01 00:00:00

  • Not all boronic acids with a five-membered cycle induce tremor, neuronal damage and decreased dopamine.

    abstract::Several striatal toxins can be used to induce motor disruption. One example is MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), whose toxicity is accepted as a murine model of parkinsonism. Recently, 3-Thienylboronic acid (3TB) was found to produce motor disruption and biased neuronal damage to basal ganglia in mi...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/j.neuro.2017.06.004

    authors: Pérez-Rodríguez M,García-Mendoza E,Farfán-García ED,Das BC,Ciprés-Flores FJ,Trujillo-Ferrara JG,Tamay-Cach F,Soriano-Ursúa MA

    更新日期:2017-09-01 00:00:00

  • Time-course of trimethyltin effects on the monoaminergic systems of the rat brain.

    abstract::The normalization of certain behavioral functions after a trimethyltin (TMT) insult indicates that compensatory processes may occur (Paule and McMillan, 1986; Bushnell and Angell, 1992). The monoamine (MA) neurons are known to be sensitive to TMT, however, a detailed temporal description of the effects is lacking. One...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:

    authors: Andersson H,Luthman J,Lindqvist E,Olson L

    更新日期:1995-07-01 00:00:00

  • Neurotoxicity of manganese: Indications for future research and public health intervention from the Manganese 2016 conference.

    abstract::Manganese is an essential trace element, but also at high levels a neurotoxicant. Manganese neurotoxicity has been extensively studied since its discovery in highly exposed workers. The International conference MANGANESE2016 held at the Icahn School of Medicine at Mount Sinai in New York provided relevant updates on m...

    journal_title:Neurotoxicology

    pub_type: 社论

    doi:10.1016/j.neuro.2018.01.002

    authors: Lucchini RG,Aschner M,Landrigan PJ,Cranmer JM

    更新日期:2018-01-01 00:00:00

  • Chronic behavioral and cognitive deficits in a rat survival model of paraoxon toxicity.

    abstract::Organophosphate (OP) compounds, including paraoxon (POX), are similar to nerve agents such as sarin. There is a growing concern that OP agents could be weaponized to cause mass civilian causalities. We have developed a rodent survival model of POX toxicity that is being used to evaluate chronic morbidity and to screen...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/j.neuro.2014.08.008

    authors: Deshpande LS,Phillips K,Huang B,DeLorenzo RJ

    更新日期:2014-09-01 00:00:00

  • Diet composition exacerbates or attenuates soman toxicity in rats: implied metabolic control of nerve agent toxicity.

    abstract::To evaluate the role of diet composition on nerve agent toxicity, rats were fed four distinct diets ad libitum for 28 d prior to challenge with 110 μg/kg (1.0 LD(50), sc) soman. The four diets used were a standard rodent diet, a choline-enriched diet, a glucose-enriched diet, and a ketogenic diet. Body weight was reco...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/j.neuro.2011.03.001

    authors: Myers TM,Langston JL

    更新日期:2011-06-01 00:00:00

  • Neural differentiation of mouse embryonic stem cells as a tool to assess developmental neurotoxicity in vitro.

    abstract::Mouse embryonic stem cells (mESCs) represent an attractive cellular system for in vitro studies in developmental biology as well as toxicology because of their potential to differentiate into all fetal cell lineages. The present study aims to establish an in vitro system for developmental neurotoxicity testing employi...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/j.neuro.2012.06.006

    authors: Visan A,Hayess K,Sittner D,Pohl EE,Riebeling C,Slawik B,Gulich K,Oelgeschläger M,Luch A,Seiler AE

    更新日期:2012-10-01 00:00:00

  • Identification of functional domains affected by developmental exposure to methylmercury: Faroe islands and related studies.

    abstract::The Faroe Islands study is a prospective study designed to assess the neurological and behavioral consequences of in utero exposure to methylmercury (meHg). Maternal exposure to meHg was through consumption of fish and intermittent higher-level exposure through pilot whale meat, while consumption of pilot whale blubbe...

    journal_title:Neurotoxicology

    pub_type: 杂志文章,评审

    doi:

    authors: Rice DC

    更新日期:2000-12-01 00:00:00

  • Inhibition of catalase activity with 3-amino-triazole enhances the cytotoxicity of the Alzheimer's amyloid-beta peptide.

    abstract::Amyloid-beta, (Abeta) is a cytotoxic peptide implicated in the pathology of Alzheimers disease. The antioxidant enzyme catalase has been suggested to protect against Abeta cytotoxicity in both neuronal and non-neuronal cell types. Inhibition of endogenous catalase using 3-amino-1,2,4-triazole (3AT) in neuronal (NT-2) ...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/s0161-813x(01)00064-x

    authors: Milton NG

    更新日期:2001-12-01 00:00:00

  • Neuroimaging in manganism.

    abstract::Neuroimaging such as magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) have been used in the last decade for investigating the neurotoxicolgy of manganese (Mn). Increased signal intensities on a T1-weighted image may reflect increased Mn deposi...

    journal_title:Neurotoxicology

    pub_type: 杂志文章,评审

    doi:10.1016/j.neuro.2005.12.002

    authors: Kim Y

    更新日期:2006-05-01 00:00:00

  • A screening programme on chronic solvent-induced encephalopathy among Dutch painters.

    abstract:BACKGROUND:Long-term exposure to organic solvents may lead to chronic solvent induced encephalopathy (CSE) in painters. In combination with reduction of exposure, a workers' health surveillance programme was developed, resulting in a three-stage CSE screening procedure for early neurobehavioural changes possibly predic...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/j.neuro.2012.05.015

    authors: Spee T,van Valen E,van Duivenbooden C,van der Laan G

    更新日期:2012-08-01 00:00:00

  • Chronic low-level lead exposure in monkeys does not affect simple reaction time.

    abstract::Simple visual reaction time was measured in a group of adult monkeys (Macaca fascicularis) dosed continuously with lead from birth onward, and in matched controls. Blood lead concentrations had been stable for 6 years at 33 micrograms/dl at the time of testing. The monkey was required to make contact with a stainless ...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:

    authors: Rice DC

    更新日期:1988-04-01 00:00:00

  • Neurochemical effects of polychlorinated biphenyls: an overview and identification of research needs.

    abstract::The PCBs are members of the halogenated hydrocarbon class of environmental chemicals that includes the dibenzofurans and dioxins. The PCBs were used over a period of 40 years for number of industrial purposes. Their appearance in the ecosystem and biological samples from wildlife, as well as documented cases of accide...

    journal_title:Neurotoxicology

    pub_type: 杂志文章,评审

    doi:

    authors: Tilson HA,Kodavanti PR

    更新日期:1997-01-01 00:00:00

  • 3-monochloropropane-1,2-diol does not cause neurotoxicity in vitro or neurobehavioral deficits in rats.

    abstract::3-monochloro-1,2-propanediol (3-MCPD) is a contaminant of acid-hydrolyzed vegetable protein. Several reports have suggested that chronic exposure to 3-MCPD could produce neurotoxicity in vitro or neurobehavioral effects in experimental animals. The present study further explored the in vitro neurotoxic effects of 0.1-...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/j.neuro.2003.08.004

    authors: Kim K,Song C,Park Y,Koh S,Kim J,Kim S,Kim Y,Kim SU,Jung H

    更新日期:2004-03-01 00:00:00

  • The feasibility of measuring manganese concentrations in human liver using neutron activation analysis.

    abstract::Manganese is an element which is required by the human body. However, as with most metals, in large amounts manganese can be toxic. People who suffer from severe manganese intoxication have symptoms similar to those of Parkinson's disease. Preclinical symptoms of manganese intoxication have recently been detected in i...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:

    authors: Arnold ML,McNeill FE,Chettle DR

    更新日期:1999-04-01 00:00:00

  • Prenatal exposure to alcohol impairs social play behavior in adolescent male mice.

    abstract::Prenatal ethanol exposure affects brain development and causes neural impairment, leading to both cognitive and behavioral consequences in the offspring. Therefore, the aim of this study was to investigate the impact of prenatal exposure to small amounts of alcohol on social play behavior in adolescent male offspring....

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/j.neuro.2020.05.007

    authors: de Ávila MAP,Gonçalves RM,Nascimento ECC,Cabral LDM,Vilela FC,Giusti-Paiva A

    更新日期:2020-07-01 00:00:00

  • Dental composite restorations and neuropsychological development in children: treatment level analysis from a randomized clinical trial.

    abstract:BACKGROUND:Resin-based dental restorations may intra-orally release their components and bisphenol A. Gestational bisphenol A exposure has been associated with poorer executive functioning in children. OBJECTIVES:To examine whether exposure to resin-based composite restorations is associated with neuropsychological de...

    journal_title:Neurotoxicology

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.neuro.2012.08.001

    authors: Maserejian NN,Trachtenberg FL,Hauser R,McKinlay S,Shrader P,Bellinger DC

    更新日期:2012-10-01 00:00:00

  • Prenatal exposure to the organophosphate pesticide chlorpyrifos and childhood tremor.

    abstract:BACKGROUND:The organophosphate insecticide chlorpyrifos (CPF), widely used for agricultural purposes, has been linked to neurodevelopmental deficits. Possible motor effects at low to moderate levels of exposure have not been evaluated. METHODS:Prenatal exposure to CPF was measured in umbilical cord blood in a sample o...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/j.neuro.2015.09.004

    authors: Rauh VA,Garcia WE,Whyatt RM,Horton MK,Barr DB,Louis ED

    更新日期:2015-12-01 00:00:00

  • Protective effect of a novel peptide against methylmercury-induced toxicity in rat primary astrocytes.

    abstract::Methylmercury (MeHg) is an environmental neurotoxicant associated with aberrant central nervous system (CNS) functions. In this study, we examined the protective effect of a novel anti-inflammatory and cytoprotective nonapeptide, termed IIIM1, against MeHg-induced toxicity in cultured rat neonatal primary astrocytes. ...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/j.neuro.2011.12.004

    authors: Wormser U,Brodsky B,Milatovic D,Finkelstein Y,Farina M,Rocha JB,Aschner M

    更新日期:2012-08-01 00:00:00

  • DNA low-density array analysis of colchicine neurotoxicity in rat cerebellar granular neurons.

    abstract::Cytoskeletal alteration is a key factor in neurodegenerative processes like Alzheimer's or Parkinson's disease. Colchicine is a microtubule-disrupting agent that binds to tubuline, inhibiting microtubule assembly, and which triggers apoptosis. The present research describes the transcriptional activation of molecules ...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/j.neuro.2007.11.007

    authors: Yeste-Velasco M,Alvira D,Sureda FX,Rimbau V,Forsby A,Pallàs M,Camins A,Folch J

    更新日期:2008-03-01 00:00:00

  • Dopamine sensitive adenylate cyclase inactivation by organolead compounds.

    abstract::Several organolead compounds have been shown to inhibit both the basal and dopamine-sensitive forms of adenylate cyclase obtained from rat caudate nucleus. The mode of action of the trisubstituted lead compounds is shown to depend upon the form of adenylate cyclase studied. The dopamine-sensitive form of adenylate cyc...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/0191-8869(82)90087-3

    authors: Wilson WE

    更新日期:1982-07-01 00:00:00

  • A potential role for altered protein phosphorylation in the mediation of developmental neurotoxicity.

    abstract::Protein phosphorylation represents a major post-translational mechanism through which numerous physiological processes are regulated. In the central nervous system, many extracellular messengers appear to exert their effects by regulating the intracellular concentration of specific second messengers which in turn acti...

    journal_title:Neurotoxicology

    pub_type: 杂志文章,评审

    doi:

    authors: O'Callaghan JP

    更新日期:1994-04-01 00:00:00

  • Prosaptide prevents paclitaxel neurotoxicity.

    abstract::Paclitaxel (Taxol), a chemotherapeutic agent used to treat breast and ovarian tumors, has been reported to induce a predominantly sensory neuropathy. Co-treatment with neurotrophic factors and paclitaxel has been proposed for preventing or reversing paclitaxel-induced peripheral neuropathy. Prosaposin, the precursor o...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:

    authors: Campana WM,Eskeland N,Calcutt NA,Misasi R,Myers RR,O'Brien JS

    更新日期:1998-04-01 00:00:00

  • Excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in experimental approaches of Parkinsonism.

    abstract::3-iodo-l-tyrosine might play a role in Parkinson's disease since this molecule is able, at high concentration, to inhibit tyrosine-hydroxylase activity, the rate-limiting enzyme in dopamine biosynthesis. The possible Parkinson-like effects of 3-iodo-l-tyrosine were tested on three experimental approaches in mice: cult...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/j.neuro.2018.06.002

    authors: Fernández-Espejo E,Bis-Humbert C

    更新日期:2018-07-01 00:00:00

  • Prenatal p,p'-DDE exposure and establishment of lateralization and spatial orientation in Mexican preschooler.

    abstract:BACKGROUND:Prenatal exposure to p,p'-DDE is associated with impairments in motor development during the first year of life, with no related repercussions on mental or motor development at 12-30 months and with impairments in cognitive areas, but not in perceptual and motor areas at preschool age. However, its associati...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/j.neuro.2014.12.011

    authors: Osorio-Valencia E,Torres-Sánchez L,López-Carrillo L,Cebrián ME,Rothenberg SJ,Hernández Chávez Mdel C,Schnaas L

    更新日期:2015-03-01 00:00:00

  • Sensitivity of immature neurons in culture to metal-induced changes in reactive oxygen species and intracellular free calcium.

    abstract::It is widely recognized that prolonged increases in reactive oxygen species (ROS) and intracellular free calcium ([Ca2+]i) are part of a signaling pathway leading to cell death. ROS production resulting in oxidative stress and disruption of calcium homeostasis leading to increases in [Ca2+]i have been described as ear...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:

    authors: Mundy WR,Freudenrich TM

    更新日期:2000-12-01 00:00:00

  • Trace element imbalances in hair and nails of Alzheimer's disease patients.

    abstract::The concentrations of 17 elements in the hair and nails of 180 Alzheimer's disease (AD) and control subjects have been determined by instrumental neutron activation analysis (INAA). Comparisons of trace element levels of properly matched AD and control groups revealed significant imbalances in the concentrations of si...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:

    authors: Vance DE,Ehmann WD,Markesbery WR

    更新日期:1988-07-01 00:00:00

  • Zinc oxide nanoparticle induced neurotoxic potential upon interaction with primary astrocytes.

    abstract::As obvious from the basic prerequisite of any particle in nanoscale, Zinc oxide nanoparticles (ZnO NPs) possess numerous tunable properties distinct from their bulk formulations. Emerging innovations in various sectors of nanotechnology are exploiting ZnO NPs largely. This inturn picks up the occasions of human exposu...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/j.neuro.2019.04.008

    authors: Sudhakaran S,Athira SS,Mohanan PV

    更新日期:2019-07-01 00:00:00

  • Synergism between insecticides permethrin and propoxur occurs through activation of presynaptic muscarinic negative feedback of acetylcholine release in the insect central nervous system.

    abstract::Although synergism between pesticides has been widely documented, the physiological mechanisms by which an insecticide synergizes another remains unclear. Toxicological and electrophysiological studies were carried out on two susceptible pest species (the mosquito Culex quinquefasciatus and the cockroach Periplaneta a...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/j.neuro.2006.01.011

    authors: Corbel V,Stankiewicz M,Bonnet J,Grolleau F,Hougard JM,Lapied B

    更新日期:2006-07-01 00:00:00

  • Protective effects of Forsythia suspense extract with antioxidant and anti-inflammatory properties in a model of rotenone induced neurotoxicity.

    abstract::The present study investigated the neuroprotective effects of Forsythia suspense extract in a rotenone-induced neurotoxic model. FS8, one of the herbal extracts, markedly protected PC12 cells against rotenone toxicity and was selected for the in vivo study. Gavage administration of FS8 (50 and 200mg/kg, but not 10mg/k...

    journal_title:Neurotoxicology

    pub_type: 杂志文章

    doi:10.1016/j.neuro.2015.09.009

    authors: Zhang S,Shao SY,Song XY,Xia CY,Yang YN,Zhang PC,Chen NH

    更新日期:2016-01-01 00:00:00