title: Differential protein expression of hepatic cells associated with MeHg exposure: deepening into the molecular mechanisms of toxicity.
abstract: Understanding the molecular mechanisms underlying MeHg toxicity and the way in which this molecule interacts with living organisms is a critical point since MeHg represents a well-known risk to ecosystems and human health. We used a quantitative proteomic approach based on stable isotopic labeling by amino acids in cell culture in combination with SDS-PAGE and nanoflow LC-ESI-LTQ for analyzing the differential protein expression of hepatic cells associated to MeHg exposure. Seventy-eight proteins were found de-regulated by more than 1.5-fold. We identified a number of proteins involved in different essential biological processes including apoptosis, mitochondrial dysfunction, cellular trafficking and energy production. Among these proteins, we found several molecules whose de-regulation has been already related to MeHg exposure, thus confirming the usefulness of our discovery approach, and new ones that helped to gain a deeper insight into the biomolecular mechanisms related to MeHg-induced toxicity. Overexpression of several HSPs and the proteasome 26S subunit itself showed the proteasome system as a molecular target of toxic MeHg. As for the interaction networks, the top ranked was the nucleic acid metabolism, where many of the identified de-regulated proteins are involved.
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, 28040, Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Cuello
authors.forename: Sonia
authors.initials: S
authors.lastname: Ramos
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Madrid
authors.forename: Jose L
authors.initials: JL
authors.lastname: Luque-Garcia
authors.forename: Carmen
authors.initials: C
authors.lastname: Cámara
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D004579:Electron Transport; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008767:Methylmercury Compounds / Q000633:toxicity*; D011506:Proteins / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D008767:Methylmercury Compounds; D011506:Proteins