Protective effect of a novel peptide against methylmercury-induced toxicity in rat primary astrocytes

Uri Wormser, Berta Brodsky, Dejan Milatovic, Yoram Finkelstein, Marcelo Farina, Joao B. Rocha, Michael Aschner

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Methylmercury (MeHg) is an environmental neurotoxicant associated with aberrant central nervous system (CNS) functions. In this study, we examined the protective effect of a novel anti-inflammatory and cytoprotective nonapeptide, termed IIIM1, against MeHg-induced toxicity in cultured rat neonatal primary astrocytes. Astrocytes were pretreated for 66h with 5μg/ml IIIM1 (4.95μM) followed by 6h exposure to MeHg (5μM). MeHg significantly increased F2-isoprostane generation, a lipid peroxidation biomarker of oxidative injury and this effect was significantly reduced upon pre-treatment with IIIM1. The MeHg-induced increase in levels of prostaglandin E2 (PGE2), biomarkers of inflammatory responses, was also decreased in the peptide-treated cells. Mass spectrometry analysis revealed no chemical or binding interaction between MeHg and IIIM1, indicating that intracellular cytoprotective mechanism of action accounts for the neuroprotection rather than direct intracellular neutralization of the neurotoxicant with the peptide. These findings point to therapeutic potential for IIIM1 in a plethora of conditions associated with reactive oxygen species (ROS) generation. The implication of these findings may prove beneficial in designing new treatment modalities that efficiently suppress neurotoxicity, triggered not only by MeHg, but also by other metals and environmental agents, as well as chronic disease conditions that inherently increase reactive radical production and inflammatory signaling.

Original languageEnglish (US)
Pages (from-to)763-768
Number of pages6
JournalNeuroToxicology
Volume33
Issue number4
DOIs
StatePublished - 2012
Externally publishedYes

Fingerprint

Biomarkers
Astrocytes
Toxicity
Rats
F2-Isoprostanes
Peptides
Neurology
Dinoprostone
Lipid Peroxidation
Mass spectrometry
Reactive Oxygen Species
Mass Spectrometry
Chronic Disease
Anti-Inflammatory Agents
Central Nervous System
Metals
Cells
Lipids
Wounds and Injuries
Therapeutics

Keywords

  • IIIM1
  • Methylmercury
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Protective effect of a novel peptide against methylmercury-induced toxicity in rat primary astrocytes. / Wormser, Uri; Brodsky, Berta; Milatovic, Dejan; Finkelstein, Yoram; Farina, Marcelo; Rocha, Joao B.; Aschner, Michael.

In: NeuroToxicology, Vol. 33, No. 4, 2012, p. 763-768.

Research output: Contribution to journalArticle

Wormser, U, Brodsky, B, Milatovic, D, Finkelstein, Y, Farina, M, Rocha, JB & Aschner, M 2012, 'Protective effect of a novel peptide against methylmercury-induced toxicity in rat primary astrocytes', NeuroToxicology, vol. 33, no. 4, pp. 763-768. https://doi.org/10.1016/j.neuro.2011.12.004
Wormser, Uri ; Brodsky, Berta ; Milatovic, Dejan ; Finkelstein, Yoram ; Farina, Marcelo ; Rocha, Joao B. ; Aschner, Michael. / Protective effect of a novel peptide against methylmercury-induced toxicity in rat primary astrocytes. In: NeuroToxicology. 2012 ; Vol. 33, No. 4. pp. 763-768.
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