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Differential protein expression of hippocampal cells associated with heavy metals (Pb, As, and MeHg) neurotoxicity: Deepening into the molecular mechanism of neurodegenerative diseases.
Karri, Venkatanaidu; Ramos, David; Martinez, Julia Bauzá; Odena, Antonia; Oliveira, Eliandre; Coort, Susan L; Evelo, Chris T; Mariman, Edwin C M; Schuhmacher, Marta; Kumar, Vikas.
Afiliação
  • Karri V; Environmental Engineering Laboratory, Departament d'Enginyeria Quimica, Universitat Rovira i Virgili, Av. Països Catalans 26, 43007 Tarragona, Spain.
  • Ramos D; Plataforma de Proteòmica, Parc Científic de Barcelona, C/Baldiri Reixac, 10-12, 08028 Barcelona, Spain.
  • Martinez JB; Plataforma de Proteòmica, Parc Científic de Barcelona, C/Baldiri Reixac, 10-12, 08028 Barcelona, Spain.
  • Odena A; Plataforma de Proteòmica, Parc Científic de Barcelona, C/Baldiri Reixac, 10-12, 08028 Barcelona, Spain.
  • Oliveira E; Unidad de Toxicologia, Parc Científic de Barcelona, C/Baldiri Reixac, 10-12, 08028 Barcelona, Spain.
  • Coort SL; Department of Bioinformatics, BiGCaT, NUTRIM, Maastricht University, 6229, ER, Maastricht, the Netherlands.
  • Evelo CT; Department of Bioinformatics, BiGCaT, NUTRIM, Maastricht University, 6229, ER, Maastricht, the Netherlands.
  • Mariman ECM; Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands.
  • Schuhmacher M; Environmental Engineering Laboratory, Departament d'Enginyeria Quimica, Universitat Rovira i Virgili, Av. Països Catalans 26, 43007 Tarragona, Spain.
  • Kumar V; Environmental Engineering Laboratory, Departament d'Enginyeria Quimica, Universitat Rovira i Virgili, Av. Països Catalans 26, 43007 Tarragona, Spain; IISPV, Hospital Universitari Sant Joan de Reus, Universitat Rovira I Virgili, Reus, Spain. Electronic address: vikas.kumar@urv.cat.
J Proteomics ; 187: 106-125, 2018 09 15.
Article em En | MEDLINE | ID: mdl-30017948
ABSTRACT
Chronic exposure to heavy metals such as Pb, As, and MeHg can be associated with an increased risk of developing neurodegenerative diseases. Our in vitro bioassays results showed the potency of heavy metals in the order of Pb < As < MeHg on hippocampal cells. The main objective of this study was combining in vitro label free proteomics and systems biology approach for elucidating patterns of biological response, discovering underlying mechanisms of Pb, As, and MeHg toxicity in hippocampal cells. The omics data was refined by using different filters and normalization and multilevel analysis tools were employed to explore the data visualization. The functional and pathway visualization was performed by using Gene ontology and PathVisio tools. Using these all integrated approaches, we identified significant proteins across treatments within the mitochondrial dysfunction, oxidative stress, ubiquitin proteome dysfunction, and mRNA splicing related to neurodegenerative diseases. The systems biology analysis revealed significant alterations in proteins implicated in Parkinson's disease (PD) and Alzheimer's disease (AD). The current proteomics analysis of three metals support the insight into the proteins involved in neurodegeneration and the altered proteins can be useful for metal-specific biomarkers of exposure and its adverse effects.

SIGNIFICANCE:

The proteomics techniques have been claimed to be more sensitive than the conventional toxicological assays, facilitating the measurement of responses to heavy metals (Pb, As, and MeHg) exposure before obvious harm has occurred demonstrating their predictive value. Also, proteomics allows for the comparison of responses between Pb, As, and MeHg metals, permitting the evaluation of potency differences hippocampal cells of the brain. Hereby, the molecular information provided by pathway and gene functional analysis can be used to develop a more thorough understanding of each metal mechanism at the protein level for different neurological adverse outcomes (e.g. Parkinson's disease, Alzheimer's diseases). Efforts are put into developing proteomics based toxicity testing methods using in vitro models for improving human risk assessment. Some of the key proteins identified can also potentially be used as biomarkers in epidemiologic studies. These heavy metal response patterns shed new light on the mechanisms of mRNA splicing, ubiquitin pathway role in neurodegeneration, and can be useful for the development of molecular biomarkers of heavy metals exposure.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Metais Pesados / Doenças Neurodegenerativas / Proteoma / Poluentes Ambientais / Hipocampo / Proteínas do Tecido Nervoso Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Proteomics Assunto da revista: BIOQUIMICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Espanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Metais Pesados / Doenças Neurodegenerativas / Proteoma / Poluentes Ambientais / Hipocampo / Proteínas do Tecido Nervoso Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Proteomics Assunto da revista: BIOQUIMICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Espanha