Insight into the neuroproteomics effects of the food-contaminant non-dioxin like polychlorinated biphenyls

Laura Brunelli, Marta LLansola, Vicente Felipo, Roberta Campagna, Luisa Airoldi, Massimiliano De Paola, Roberto Fanelli, Alessandro Mariani, Marco Mazzoletti, Roberta Pastorelli

Research output: Contribution to journalArticle

Abstract

Recent studies showed that food-contaminant non-dioxin-like polychlorinated biphenyls (NDL-PCBs) congeners (PCB52, PCB138, PCB180) have neurotoxic potential, but the cellular and molecular mechanisms underlying neuronal damage are not entirely known. The aim of this study was to assess whether in-vitro exposure to NDL-PCBs may alter the proteome profile of primary cerebellar neurons in order to expand our knowledge on NDL-PCBs neurotoxicity. Comparison of proteome from unexposed and exposed rat cerebellar neurons was performed using state-of-the-art label-free semi-quantitative mass-spectrometry method. We observed significant changes in the abundance of several proteins, that fall into two main classes: (i) novel targets for both PCB138 and 180, mediating the dysregulation of CREB pathways and ubiquitin-proteasome system; (ii) different congeners-specific targets (alpha-actinin-1 for PCB138; microtubule-associated-protein-2 for PCB180) that might lead to similar deleterious consequences on neurons cytoskeleton organization. Interference of the PCB congeners with synaptic formation was supported by the increased expression of pre- and post-synaptic proteins quantified by western blot and immunocytochemistry. Expression alteration of synaptic markers was confirmed in the cerebellum of rats developmentally exposed to these congeners, suggesting an adaptive response to neurodevelopmental toxicity on brain structures. As such, our work is expected to lead to new insights into the mechanisms of NDL-PCBs neurotoxicity.

Original languageEnglish
Pages (from-to)2417-2430
Number of pages14
JournalJournal of Proteomics
Volume75
Issue number8
DOIs
Publication statusPublished - Apr 18 2012

Keywords

  • Network analysis
  • Non-dioxin like PCBs
  • Primary neurons
  • Proteomics
  • Synaptic proteins

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

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    Brunelli, L., LLansola, M., Felipo, V., Campagna, R., Airoldi, L., De Paola, M., Fanelli, R., Mariani, A., Mazzoletti, M., & Pastorelli, R. (2012). Insight into the neuroproteomics effects of the food-contaminant non-dioxin like polychlorinated biphenyls. Journal of Proteomics, 75(8), 2417-2430. https://doi.org/10.1016/j.jprot.2012.02.023