Cytotoxic effects of copper overload on human-derived lung and liver cells in culture

Background: Copper (Cu) is an essential trace metal used as a catalytic cofactor for many enzymes. However, it can have nocive effects when it participates in the Fenton reaction, producing reactive oxygen species (ROS). Excess Cu is present in the plasma of patients with diseases in which cell surv...

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Detalles Bibliográficos
Autores principales: Arnal, Nathalie, Tacconi de Alaniz, María Josefa, Marra, Carlos Alberto
Formato: Articulo
Lenguaje:Inglés
Publicado: 2012
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/97711
https://ri.conicet.gov.ar/11336/81749
Aporte de:
id I19-R120-10915-97711
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Bioquímica
Apoptosis
Cell division
Copper
Liver
Lung
Oxidative stress
spellingShingle Bioquímica
Apoptosis
Cell division
Copper
Liver
Lung
Oxidative stress
Arnal, Nathalie
Tacconi de Alaniz, María Josefa
Marra, Carlos Alberto
Cytotoxic effects of copper overload on human-derived lung and liver cells in culture
topic_facet Bioquímica
Apoptosis
Cell division
Copper
Liver
Lung
Oxidative stress
description Background: Copper (Cu) is an essential trace metal used as a catalytic cofactor for many enzymes. However, it can have nocive effects when it participates in the Fenton reaction, producing reactive oxygen species (ROS). Excess Cu is present in the plasma of patients with diseases in which cell survival is crucial. In order to investigate the effect of Cu overload on the induction of cellular damage we chose two human cell lines derived from liver (HepG2) and lung (A-549) as representative cells exposed to exogenous (polluted air) and/or endogenous (systemic) Cu overload. Methods: We studied ROS production using thiobarbituric acid reactive substances (TBARS) and fluorimetric measurements with dichlorofluorescein, cell viability by the trypan dye exclusion test, the methyltetrazolium (MTT) and lactate dehydrogenase leakage (LDH) assays, various cytotoxic indexes, and caspasa-3 and calpain-dependent activation as the main signals involved in the apoptosis pathway. Results: Cu overload induces cell death by a differential activation of calpains (m- and μ-) and caspase-3, and modifies various proliferative indexes in a cell-type and concentration-dependent manner. The involvement of these two protease systems and the response of the two main Cu homoestatic proteins ceruloplasmin and metallothioneins are specific to each cell type. We demonstrated that Cu can trigger cell death by activation of specific protease systems and modify various proliferative indexes in a cell-type and concentration-dependent manner. General significance: These findings contribute to understanding the diverse effects of Cu overload on the pathogenesis of human diseases like cancer, cirrhosis and degenerative disorders.
format Articulo
Articulo
author Arnal, Nathalie
Tacconi de Alaniz, María Josefa
Marra, Carlos Alberto
author_facet Arnal, Nathalie
Tacconi de Alaniz, María Josefa
Marra, Carlos Alberto
author_sort Arnal, Nathalie
title Cytotoxic effects of copper overload on human-derived lung and liver cells in culture
title_short Cytotoxic effects of copper overload on human-derived lung and liver cells in culture
title_full Cytotoxic effects of copper overload on human-derived lung and liver cells in culture
title_fullStr Cytotoxic effects of copper overload on human-derived lung and liver cells in culture
title_full_unstemmed Cytotoxic effects of copper overload on human-derived lung and liver cells in culture
title_sort cytotoxic effects of copper overload on human-derived lung and liver cells in culture
publishDate 2012
url http://sedici.unlp.edu.ar/handle/10915/97711
https://ri.conicet.gov.ar/11336/81749
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AT tacconidealanizmariajosefa cytotoxiceffectsofcopperoverloadonhumanderivedlungandlivercellsinculture
AT marracarlosalberto cytotoxiceffectsofcopperoverloadonhumanderivedlungandlivercellsinculture
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