Data: 19/04/17 (Quarta-Feira)
Hora: 12h50
Local: Bloco Beta, Auditório A005 (campus São Bernardo do Campo)
Palestrante: Prof. Dr. Raúl Bonne Hernández (UNIFESP)
Tema: The role of manganese in neurotoxicity and neurodegenerative disorders – Lessons from yeast to human
Manganese (Mn) is an essential element for living organisms, playing an important role in nervous system function, bone mineralization, protein and energy metabolism, metabolic regulation and cellular protection. Nevertheless, chronic and/or acute exposure for this metal, mainly during early life stages can lead to neurotoxicity, parkinsonian disorders and other neurodegenerative disorders (depression, movement disorders and dementia)by unclear mechanisms. For that reason, we hypothesizedif the adverse outcome pathways induced by manganese species are conserved cross-species, this must improve the understanding of the unclear neuro (toxicological) mechanisms of this metal and its involving in neurodegeneration. Therefore, this study was to investigate the mechanisms mediating the toxic effects of the manganese in phylogeneticinterconnected biological models such as Saccharomyces cerevisiae(yeast), Danio rerio(zebrafish),Mus musculus(primary cultures of cerebellar granular cells-CGC) and Homo sapiens(human neuroblastoma SH-SY5Y cell line). The biological models were exposed for chemical species of manganese, followed ofbioanalytical approaches such as cell viability-MTT-assay,sensitivity-gene-screening assay and translation protein efficiency in yeast, semi-quantitative proteomics -tandem mass tag (TMT), transcriptomics (human gene expression microarray Kit (Agilent) and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), metallomics (metal bioaccumulation, metal homeostasis and its potential link with the proteome), phenomicsand bioinformatics (meta-analysis of microarray-based gene expression studies, gene ontology-GOanalysisand prediction of protein-protein interaction -PPI).The identification of peptides in databases for TMT was using the Protein Discovery of Thermo-Instruments software. The GO analysis and PPI were performed in the string-database.Results wereexpressed as mean ± SEM of at least 3 experiments; LC50 and statistically significant differences were estimated by ANOVA (analysis of variance followed by Bonferroni’s tests) and, alternative t-student, using the GraphPad Prism (GraphPad 4.0 Software Inc, San Diego, CA, USA). The study identified that independently of chemical speciation the manganese inducesfrom yeast to humanmetal dyshomeostasis;alterations of multiple signaling pathways; which can elicit or silence the protein biosynthesis, a process energetically dependentand associated with the proteasomeas well as similar neurobehavioural alterations (locomotive and cognition impairment) endpoints of neurotoxicological events.Altogether, these findings contribute to a putative adverse outcome pathways (AOP) framework relevant for understanding the role of manganese neurotoxicity, neurodegenerative disorder such as Alzheimer´s disease, Huntinton´s disease, Parkinson´s disease and Parkinsonismand environmental neurotoxicology risk assessment.
Raúl Bonne Hernández
Possui graduação em Licenciatura em Química (2000) e Mestrado em Manejo Integrado de Zonas Costeiras, ambos pela Universidade de Oriente (2002-2003). Doutorado em Química pela Universidade de São Paulo (2006-2009), Pós-Doutorado em Bioquímica pela Universidade de São Paulo (2010), com estágios em Neurotoxicologia no IIBB-CSIC-Espanha (6 meses, 2008) e em toxicogenômica na UFZ-Alemanha (3 meses, 2009).
Professor de Química Ambiental, Química Geral e Toxicologia na Universidade Federal de São Paulo. Tem experiência em Química Bioinorgânica, principalmente em Especiação Química, Fracionamento Químico, e Toxicogenômica aplicadas em Estudos de Neuro (toxicologia) Ambiental de Metais com os modelo experimentais (paulistinha) Zebrafish, culturas primaria de células granulares do cerebelo e saccharomyces cerevisiae (yeast). Professor visitante na Universidade de Carleton, Canadá (2016-2017).
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