title: Molecular regulations induced by acrolein in neuroblastoma SK-N-SH cells: relevance to Alzheimer's disease.
abstract: Acrolein is the most reactive aldehyde among the by-products of lipid peroxidation. Growing evidence indicates that acrolein may play an important role in the pathogenesis of Alzheimer's disease (AD). In AD, levels of acrolein are significantly higher in hippocampus and temporal cortex regions of the brain. However, little is known about its toxicity in neuronal cells. Using the neuroblastoma cell line SK-N-SH, our results show that acrolein is toxic from 10 μM, but its toxicity does not induce the activation of caspase-3 and DNA fragmentation. Protein carbonylation and 4-hydroxynonenal levels were increased after 0.5 hr and 1 hr of treatment, respectively. Furthermore acrolein induced a biphasic effect on glutathione levels with a rapid depletion followed by a progressive increase. We have further investigated the regulation of different redox signaling pathways. A treatment with 10 μM of acrolein for 30 min activated NFκB while this activation was suppressed after a 24 hrs of treatment. In contrast, Nrf2 was activated only after 24 hrs of acrolein exposure. Consequently, the expression of heme oxygenase-1 and γ-glutamyl-cysteine-synthase were elevated after 24 hrs of acrolein treatment. Sirt-1 was also upregulated after 24 hrs of acrolein treatment. The p66Shc and ERK1/2 proteins are known to be involved in oxidative stress. Acrolein, at 10 μM, induced the phosphorylation of p66Shc and ERK1/2 only after a short period of treatment. Collectively, these data strengthen the contribution of acrolein in the induction of oxidative stress as observed in mild cognitive impairment and in AD brain.
authors.affiliation: INRS-Institut Armand Frappier, Québec, Canada.
authors.forename: Thanh Nam
authors.initials: TN
authors.lastname: Dang
authors.forename: Madeleine
authors.initials: M
authors.lastname: Arseneault
authors.forename: Neven
authors.initials: N
authors.lastname: Zarkovic
authors.forename: Georg
authors.initials: G
authors.lastname: Waeg
authors.forename: Charles
authors.initials: C
authors.lastname: Ramassamy
mesh_terms: D000171:Acrolein / Q000633:toxicity*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018736:DNA Adducts / Q000096:biosynthesis; D053938:DNA Fragmentation / Q000187:drug effects; D005609:Free Radicals / Q000633:toxicity; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology
chemical_list: D018736:DNA Adducts; D005609:Free Radicals; D000171:Acrolein