Effect of copper on extracellular levels of key pro-inflammatory molecules in hypothalamic GN11 and primary neurons

Copper dyshomeostasis is responsible for the neurological symptoms observed in the genetically inherited copper-dependent disorders (e.g., Menkes’ and Wilson's diseases), but it has been also shown to have an important role in neurodegenerative diseases such as Alzheimer disease, prion diseases...

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Veröffentlicht in:Neurotoxicology (Park Forest South) 2009-07, Vol.30 (4), p.605-612
Hauptverfasser: Spisni, Enzo, Valerii, Maria Chiara, Manerba, Marcella, Strillacci, Antonio, Polazzi, Elisabetta, Mattia, Toni, Griffoni, Cristiana, Tomasi, Vittorio
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container_issue 4
container_start_page 605
container_title Neurotoxicology (Park Forest South)
container_volume 30
creator Spisni, Enzo
Valerii, Maria Chiara
Manerba, Marcella
Strillacci, Antonio
Polazzi, Elisabetta
Mattia, Toni
Griffoni, Cristiana
Tomasi, Vittorio
description Copper dyshomeostasis is responsible for the neurological symptoms observed in the genetically inherited copper-dependent disorders (e.g., Menkes’ and Wilson's diseases), but it has been also shown to have an important role in neurodegenerative diseases such as Alzheimer disease, prion diseases, Parkinson's disease and amyotrophic lateral sclerosis. It is widely accepted that increased extracellular copper levels contribute to neuronal pathogenic process by increasing the production of dangerous radical oxygen species, but the existence of other molecular mechanisms explaining copper neurotoxicity has not been investigated yet. By using a cellular model based on hypothalamic GN11 cultured neurons exposed to copper supplementation and by analysing the cell conditioned media, we try here to identify new molecular events explaining the association between extracellular copper accumulation and neuronal damages. We show here that increased extracellular copper levels produce a wide complex of alterations in the neuronal extracellular environment. In particular, copper affects the secretion of molecules involved in the protection of neurons against oxidative stress, such as cyclophilin A (CypA), or of molecules capable of shifting neuronal cells towards a pro-inflammatory state, such as IL-1α, IL-12, Rantes, neutrophil gelatinase-associated lipocalin (NGAL) and secreted protein acidic and rich in cysteine (SPARC). Copper pro-inflammatory properties have been confirmed by using primary neurons.
doi_str_mv 10.1016/j.neuro.2009.03.005
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subjects Acute-Phase Proteins - metabolism
Analysis of Variance
Animals
Animals, Newborn
Biological and medical sciences
Cells, Cultured
Cerebral Cortex - cytology
Chemical and industrial products toxicology. Toxic occupational diseases
Copper
Copper - metabolism
Copper - pharmacology
Culture Media, Conditioned - chemistry
Cyclophilin A
Cyclophilin A - metabolism
Cytokines - metabolism
Dose-Response Relationship, Drug
Extracellular Fluid - drug effects
Extracellular Fluid - metabolism
Hypothalamus - cytology
Inflammation
Lipocalins - metabolism
Medical sciences
Metals and various inorganic compounds
Mice
Neurons - drug effects
Neutrophil gelatinase-associated lipocalin (NGAL)
Osteonectin - metabolism
Peptide Mapping
Proto-Oncogene Proteins - metabolism
Rats
Rats, Wistar
Secreted protein acidic and rich in cysteine (SPARC)
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods
Spectrophotometry, Atomic
Toxicology
Trace Elements - metabolism
Trace Elements - pharmacology
title Effect of copper on extracellular levels of key pro-inflammatory molecules in hypothalamic GN11 and primary neurons
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