NDLI: A quantitative proteomic approach for unveiling novel mechanisms associated with MeHg-induced toxicity: effects on the methylation cycle

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A quantitative proteomic approach for unveiling novel mechanisms associated with MeHg-induced toxicity: effects on the methylation cycle

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Toxicology Research Vol -4

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Toxicology Research Vol -1

A quantitative proteomic approach for unveiling novel mechanisms associated with MeHg-induced toxicity: effects on the methylation cycle

Content Provider	Royal Society of Chemistry (RSC)
Author	Cabezas-Sanchez, Pablo Luque-Garcia, Jose L. Garcia-Calvo, Estefania Camara, Carmen
Copyright Year	2016
Abstract	Methylmercury (MeHg) is still a major threat for human health and the environment due to its extremely high toxicity that mainly affects the nervous system. Despite the great efforts made during the last few decades, the specific molecular mechanisms involved in MeHg-induced toxicity are still not completely unveiled. In this work we explored such mechanisms using neuroblastoma cells (Neuro-2a) and SILAC as a quantitative proteomic approach. We found that exposure of Neuro-2a cells to 2 mg L−1 MeHg for 8 h decreased the cell viability to 70% and caused significant changes in the morphology of the cells, specially regarding neurite development. Our proteomic results showed different proteins altered upon MeHg exposure that helped to identify pathways related to the toxicity exerted by MeHg. Specifically, we have found that MeHg affects the methylation cycle by inhibiting the expression of key enzymes including MTHFD1 and MTR. Moreover, we demonstrate that inhibition of MTHFD1 is not observed when exposing the cells to inorganic Hg and other heavy metals such as Pb or Cu. Thus, this work sets the stage for dissecting a specific molecular mechanism for MeHg-induced toxicity.
Starting Page	291
Ending Page	302
Page Count	12
File Format	HTM / HTML PDF
ISSN	2045452X
Volume Number	5
Issue Number	1
Journal	Toxicology Research
DOI	10.1039/c5tx00354g
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Stable isotope labeling by amino acids in cell culture Neurite MTHFD1 Methylmercury Lead Nervous system Neuroblastoma Methionine synthase Methylation
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Toxicology

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