title: Acrolein activates cell survival and apoptotic death responses involving the endoplasmic reticulum in A549 lung cells.
abstract: Acrolein, a highly reactive α,β-unsaturated aldehyde, is a product of endogenous lipid peroxidation. It is a ubiquitous environmental pollutant that is generated mainly by smoke, overheated cooking oil and vehicle exhaust. Acrolein damages cellular proteins, which could lead to accumulation of aberrantly-folded proteins in the endoplasmic reticulum (ER). This study determines the mechanisms involved in acrolein-induced apoptosis mediated by the ER and possible links with the ER stress response in human A549 lung cells. The exposure of cells to acrolein (15-50μM) for shorter times of 15 to 30min activated several ER stress markers. These included the ER chaperone protein BiP and the three ER sensors: (i) the survival/rescue molecules protein kinase RNA (PKR)-like ER kinase (PERK) and eukaryotic initiation factor 2 alpha (eIF2α) were phosphorylated; (ii) cleavage of activating transcription factor 6 (ATF6) occurred, and (iii) inositol-requiring protein-1 alpha (IRE1α) was phosphorylated. Acrolein (25-50μM) caused apoptotic cell death mediated by the ER after 2h, which was characterised by the induction of CHOP and activation of ER proteases calpain and caspase-4. Calpain and caspase-7 were the initiating factors for caspase-4 activation in acrolein-induced apoptosis. These results increase our knowledge about cellular responses to acrolein in lung cells, which have implications for human health.
authors.affiliation: Département des Sciences Biologiques (TOXEN), Université du Québec à Montréal, CP 8888, Succursale Centre-ville, Montréal, Québec H3C 3P8, Canada.
authors.forename: André
authors.initials: A
authors.lastname: Tanel
authors.affiliation: Département des Sciences Biologiques (TOXEN), Université du Québec à Montréal, CP 8888, Succursale Centre-ville, Montréal, Québec H3C 3P8, Canada.
authors.forename: Pragathi
authors.initials: P
authors.lastname: Pallepati
authors.affiliation: Département des Sciences Biologiques (TOXEN), Université du Québec à Montréal, CP 8888, Succursale Centre-ville, Montréal, Québec H3C 3P8, Canada.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bettaieb
authors.affiliation: Département des Sciences Biologiques (TOXEN), Université du Québec à Montréal, CP 8888, Succursale Centre-ville, Montréal, Québec H3C 3P8, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Morin
authors.affiliation: Département des Sciences Biologiques (TOXEN), Université du Québec à Montréal, CP 8888, Succursale Centre-ville, Montréal, Québec H3C 3P8, Canada. Electronic address: averill.diana@uqam.ca.
authors.forename: Diana A
authors.initials: DA
authors.lastname: Averill-Bates
mesh_terms: D000171:Acrolein / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000171:Acrolein
keywords: Acrolein; Apoptosis; Calpain; Caspase; ER stress; Endoplasmic reticulum