A brain proteome profile in rats exposed to methylmercury or thimerosal (ethylmercury)

Abstract

Exposure to organomercurials has been associated with harmful effects on the central nervous system (CNS). However, the mechanisms underlying organomercurial-mediated neurotoxic effects need to be elucidated. Exposure to toxic elements may promote cellular modifications such as alterations in protein synthesis in an attempt to protect tissues and organs from damage. In this context, the use of a "proteomic profile" is an important tool to identify potential early biomarkers or targets indicative of neurotoxicity. The aim of this study was to investigate potential modifications in rat cerebral cell proteome following exposure to methylmercury (MeHg) or ethylmercury (EtHg). For MeHg exposure, animals were administered by gavage daily 140 µg/kg/d of Hg (as MeHg) for 60 d and sacrificed 24 h after the last treatment. For EtHg exposure, 800 µg/kg/d of Hg (as EtHg) was given intramuscularly (im) in a single dose and rats were sacrificed after 4 h. Control groups received saline either by gavage or im. After extraction of proteins from whole brain samples and separation by two-dimensional electrophoresis (2-DE), 26 differentially expressed proteins were identified from exposed animals by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF/TOF). Both MeHg and EtHg exposure induced an overexpression of calbindin, a protein that acts as a neuroprotective agent by (1) adjusting the concentration of Ca(2+) within cells and preventing neurodegenerative diseases and (2) decreasing expression of glutamine synthetase, a crucial protein involved in regulation of glutamate concentration in synaptic cleft. In contrast, expression of superoxide dismutase (SOD), a protein involved in antioxidant defense, was elevated in brain of MeHg-exposed animals. Taken together, our data provide new valuable information on the possible molecular mechanisms associated with MeHg- and EtHg-mediated toxicity in cerebral tissue. These observed protein alterations may be considered as biomarkers candidates for biological monitoring of organomercurial poisoning.

Methylmercury Induced Neurotoxicity and the Influence of Selenium in the Brains of Adult Zebrafish (Danio rerio)

“…This is the first study to use proteomics profiling tools on zebrafish as a model species to assess MeHg induced neurotoxicity. The MeHg induced brain proteome changes were similar in magnitude with those reported in other proteomics studies exploring MeHg exposure in the brain [11,20,26,27]. However, we found few similarities between this and other similar studies in relation to specific proteins affected by MeHg.…”

“…The neurotoxic effects of MeHg have previously been investigated in vivo using proteomics approaches in fish, rodents, and monkeys [11,20,26,27]. This is the first study to use proteomics profiling tools on zebrafish as a model species to assess MeHg induced neurotoxicity.…”

“…Several proteins that were predominately up-regulated by SeMet exposure in the current study were affected by MeHg exposure in other studies, where they were predominately downregulated. These include, for example, vimentin (VIM) and members of the tubulin (TUB), proteasome 26S subunit, non-ATPase (PSM), fructose-bisphosphate aldolase (ALDO), and glutathione peroxidase (GPX) families [26,27]. The three top ranked canonical pathways associated with the SeMet-induced proteome were also amongst those most affected by MeHg exposure.…”

Oxidative Biochemistry Disbalance and Changes on Proteomic Profile in Salivary Glands of Rats Induced by Chronic Exposure to Methylmercury

“…Studies appoint that MeHg induces multiple effects within cell homeostasis. MeHg is able to induce cell death [ 37 ], impairment on cell proliferation and differentiation [ 38 ], disorganization of cytoskeleton [ 39 , 40 ], DNA mutation [ 41 ], impairments on transcriptome [ 42 ], and proteome [ 43 ]. In addition, according to the literature, these damages on biological processes and structures could be associated with oxidative/nitrosative biochemistry misbalance due to oxidative stress.…”

Biomarkers of mercury toxicity: Past, present, and future trends

“…The identification of single- or, preferentially, multi-targets of Hg that might represent early markers of effect to low levels of mercurial exposure is highly desirable, yet a difficult task to achieve. “Proteomic profiling” has recently emerged as a strategy capable of identifying early targets of Hg that may potentially be employed as new biomarkers (de Oliveira Souza et al, 2016) albeit this toxicoproteomic approach remains incipient (Merrick, 2006). Thus, future studies need to be conducted in experimental models of intoxication with mercurials encompassing Hg speciation in plasma, blood and target tissues.…”