Differential protein expression of hippocampal cells associated with heavy metals (Pb, As, and MeHg) neurotoxicity: Deepening into the molecular mechanism of neurodegenerative diseases

Identifier:  imarina:5132977

Handle: https://hdl.handle.net/20.500.11797/imarina5132977

Authors:  Karri, V; Ramos, D; Martinez, JB; Odena, A; Oliveira, E; Coort, SL; Evelo, CT; Mariman, ECM; Schuhmacher, M; Kumar, V

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.