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

Enzo Spisni, Maria Chiara Valerii, Marcella Manerba, Antonio Strillacci, Elisabetta Polazzi, Toni Mattia, Cristiana Griffoni, Vittorio Tomasi

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)605-612
Number of pages8
JournalNeuroToxicology
Volume30
Issue number4
DOIs
Publication statusPublished - Jul 2009

Fingerprint

Neurons
Copper
Molecules
Cyclophilin A
Menkes Kinky Hair Syndrome
Neurodegenerative diseases
Lipocalins
Gelatinases
Hepatolenticular Degeneration
Prion Diseases
Oxidative stress
Prions
Amyotrophic Lateral Sclerosis
Interleukin-12
Conditioned Culture Medium
Interleukin-1
Neurodegenerative Diseases
Cysteine
Parkinson Disease
Reactive Oxygen Species

Keywords

  • Copper
  • Cyclophilin A
  • Inflammation
  • Neutrophil gelatinase-associated lipocalin (NGAL)
  • Secreted protein acidic and rich in cysteine (SPARC)

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Spisni, E., Valerii, M. C., Manerba, M., Strillacci, A., Polazzi, E., Mattia, T., ... Tomasi, V. (2009). Effect of copper on extracellular levels of key pro-inflammatory molecules in hypothalamic GN11 and primary neurons. NeuroToxicology, 30(4), 605-612. https://doi.org/10.1016/j.neuro.2009.03.005

Effect of copper on extracellular levels of key pro-inflammatory molecules in hypothalamic GN11 and primary neurons. / Spisni, Enzo; Valerii, Maria Chiara; Manerba, Marcella; Strillacci, Antonio; Polazzi, Elisabetta; Mattia, Toni; Griffoni, Cristiana; Tomasi, Vittorio.

In: NeuroToxicology, Vol. 30, No. 4, 07.2009, p. 605-612.

Research output: Contribution to journalArticle

Spisni, E, Valerii, MC, Manerba, M, Strillacci, A, Polazzi, E, Mattia, T, Griffoni, C & Tomasi, V 2009, 'Effect of copper on extracellular levels of key pro-inflammatory molecules in hypothalamic GN11 and primary neurons', NeuroToxicology, vol. 30, no. 4, pp. 605-612. https://doi.org/10.1016/j.neuro.2009.03.005
Spisni, Enzo ; Valerii, Maria Chiara ; Manerba, Marcella ; Strillacci, Antonio ; Polazzi, Elisabetta ; Mattia, Toni ; Griffoni, Cristiana ; Tomasi, Vittorio. / Effect of copper on extracellular levels of key pro-inflammatory molecules in hypothalamic GN11 and primary neurons. In: NeuroToxicology. 2009 ; Vol. 30, No. 4. pp. 605-612.
@article{97315ea632e14ce59fce2d00020bde19,
title = "Effect of copper on extracellular levels of key pro-inflammatory molecules in hypothalamic GN11 and primary neurons",
abstract = "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.",
keywords = "Copper, Cyclophilin A, Inflammation, Neutrophil gelatinase-associated lipocalin (NGAL), Secreted protein acidic and rich in cysteine (SPARC)",
author = "Enzo Spisni and Valerii, {Maria Chiara} and Marcella Manerba and Antonio Strillacci and Elisabetta Polazzi and Toni Mattia and Cristiana Griffoni and Vittorio Tomasi",
year = "2009",
month = "7",
doi = "10.1016/j.neuro.2009.03.005",
language = "English",
volume = "30",
pages = "605--612",
journal = "NeuroToxicology",
issn = "0161-813X",
publisher = "Elsevier",
number = "4",

}

TY - JOUR

T1 - Effect of copper on extracellular levels of key pro-inflammatory molecules in hypothalamic GN11 and primary neurons

AU - Spisni, Enzo

AU - Valerii, Maria Chiara

AU - Manerba, Marcella

AU - Strillacci, Antonio

AU - Polazzi, Elisabetta

AU - Mattia, Toni

AU - Griffoni, Cristiana

AU - Tomasi, Vittorio

PY - 2009/7

Y1 - 2009/7

N2 - 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.

AB - 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.

KW - Copper

KW - Cyclophilin A

KW - Inflammation

KW - Neutrophil gelatinase-associated lipocalin (NGAL)

KW - Secreted protein acidic and rich in cysteine (SPARC)

UR - http://www.scopus.com/inward/record.url?scp=67650812503&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650812503&partnerID=8YFLogxK

U2 - 10.1016/j.neuro.2009.03.005

DO - 10.1016/j.neuro.2009.03.005

M3 - Article

C2 - 19635393

AN - SCOPUS:67650812503

VL - 30

SP - 605

EP - 612

JO - NeuroToxicology

JF - NeuroToxicology

SN - 0161-813X

IS - 4

ER -