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Proteomic and metallomic studies for understanding the developmental neurotoxicity induced by manganese-containing pesticides

Grant number: 14/08990-2
Support type:Scholarships abroad - Research
Effective date (Start): June 15, 2014
Effective date (End): September 14, 2014
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal Investigator:Raúl Bonne Hernández
Grantee:Raúl Bonne Hernández
Host: Cristina Suñol Esquirol
Home Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
Local de pesquisa : Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spain  

Abstract

Manganese (Mn) is essential 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 and dementia (cognitive and neurobehavioral impairment). Despite, the history of science register more than 100 year of studies about Mn neurotoxicity, few biomarkers are correlated with manganese exposure, the mechanism for these events are still unclear and consequently the treatments for Mn poison are not satisfactories at today. For that reason, more studies are necessaries, where toxicogenomic approaches can be an option to improve these fields of study. Toxicogenomic can to include several, novel and integrated approaches such as genomic, transcritomic, proteomic, metallomic and metabolomic strategies associated with old pathological and toxicological techniques. Recently, our identified several genes (bcat2, cenpj, dpp4, eif2s1, ell2, erbb2ip, mmp2, myl6, sgce, slc14a2 and tcea3) that are deregulated in zebrafish larve of 120 hours post fertilization (hpf) after exposure for chemical species of manganese (48-120 hpf). These genes are associated with protein impairment and potentially with dementia (data in process to publish). However, not all alterations in gene expression should be viewed as responses to a toxin and other approaches are necessaries to understand the mode of action of the manganese-induced developmental neurotoxicity. Precisely, we are proposing to study this phenomenon by both tactics proteomic (large-scale study of proteins, particularly their structures and functions) and metallomic (comprehensive analysis of the entirety of metal and metalloid species within a cell or tissue type - metal speciation". Therefore, metallomics can be considered a branch metabolomics, even though the metals are not typically considered as metabolites). These studies will conduced on of two developmental models (zebrafish larvae and cerebellar granule cell) after exposure for chemical species of manganese. (AU)