Differential protein expression of hepatic cells associated with MeHg exposure: deepening into the molecular mechanisms of toxicity

作者：Cuello Susana; Ramos Sonia; Madrid Yolanda; Luque Garcia Jose L^*; Camara Carmen

来源：Analytical and Bioanalytical Chemistry, 2012, 404(2): 315-324.

DOI：10.1007/s00216-012-6042-3

• Bioanalytical methods
• Proteomics
• Toxicology
• Heavy metals
• Mass spectrometry

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.

• 出版日期2012-8