Proteome profiling reveals regional protein alteration in cerebrum of common marmoset (Callithrix jacchus) exposed to methylmercury

Toxicology. 2016 Mar 10;347-349:29-39. doi: 10.1016/j.tox.2016.03.001. Epub 2016 Mar 21.

Abstract

Methylmercury (MeHg) is known to selectively damage the calcarine and precentral cortices along deep sulci and fissures in adult cases, but the detailed mechanism is still unclear. This study aims to identify and analyze the differential proteome expression in two regions of the cerebrum (the frontal lobe and the occipital lobe including the calcarine sulcus) of the common marmoset exposed to MeHg using a shot-gun proteomic approach. A total of 1045 and 1062 proteins were identified in the frontal lobe (FL) and occipital lobe (OL), of which, 62 and 89 proteins were found significantly changed with MeHg exposure. Functional enrichment/depletion analysis showed that the lipid metabolic process and proteolysis were affected in both two lobes. Functional changes in FL were characterized in cell cycle and cell division, sulfur compound metabolic process, microtubule-based process and glycerolipid metabolic process. In comparison, proteins were enriched in the functions of transport, carbohydrate metabolic process, chemical caused homeostasis and regulation of body fluid levels in OL. Pathway analysis predicted that vasopressin-regulated water reabsorption was disturbed in MeHg-treated FL. Our results showed that MeHg induced regional specific protein changes in FL and OL but with similar endpoint effects such as energy diminish and disruption of water transport. APOE and GPX1 were shown to be possible key proteins targeted by MeHg leading to multiple functional changes in OL. This is the first report of the whole proteome changes of primate cerebrum for MeHg neurotoxicity, and the results will contribute to the understanding of molecular basis of MeHg intoxication in humans.

Keywords: Cerebrum; Methylmercury; Neurotoxicity; Primates; Proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Callithrix
  • Cerebrum / drug effects*
  • Cerebrum / metabolism*
  • Female
  • Gene Expression Profiling / methods*
  • Humans
  • Methylmercury Compounds / toxicity*
  • Proteome / genetics
  • Proteome / metabolism*

Substances

  • Methylmercury Compounds
  • Proteome