Affiliations: [a] INRS-Institut Armand Frappier, Laval, QC, Canada | [b] Department of Medical Biology, Faculty of Medicine, Laval University, QC, Canada
Correspondence:
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Correspondence to: Prof. Charles Ramassamy, INRS-Institut Armand Frappier, 531, boul. des Prairies, Laval, QC, H7 V 1B7, Canada. Tel.: +1 450 687 5010; Fax: +1 450 687 5510; E-mail: Charles.Ramassamy@iaf.inrs.ca.
Abstract: Lipid peroxidation leads to the formation of a number of by-products including acrolein. In brain from patients with Alzheimer's disease (AD), acrolein was found to be elevated in vulnerable regions. Astrocytes contribute to a variety of neuronal functions but the toxicity of acrolein in astroglial cells remains unknown. Using the rat primary astroglial cells, our results show that acrolein is toxic from 15 μM. Acrolein induced a biphasic effect on glutathione (GSH) levels with a depletion after 30 min of treatment followed by a progressive increase 24 hrs after exposure while the expression of γ-glutamyl-cysteine-synthase (γ-GCS) was induced. Protein carbonyls levels were significantly higher with all tested concentrations of acrolein. We have further investigated the effect of acrolein on the regulation of different redox-sensitive signaling pathways. A treatment with 20 μM of acrolein for 30 min activated NF-κB, Nrf2, and heme oxygenase-1 while after 24 hrs of exposure, their induction was observed with the subtoxic and toxic concentrations of acrolein except for NF-κB. Sirt-1 was also up-regulated after 24 hrs of exposure with acrolein. Acrolein also induced the phosphorylation of p66shc and of ERK1/2 after 30 min of treatment. Our results provide evidence that acrolein is a potent inducer of redox-sensitive pathways in astrocytes with a differential regulation after a short or a long term period of exposure to overcome cell death. Considering the crucial role of astrocytes in the brain, these results demonstrated that acrolein could disrupt neuronal functions and synaptic homeostasis by provoking dysfunctional or loss of astrocytes.
