title: Protein alkylation by the α,β-unsaturated aldehyde acrolein. A reversible mechanism of electrophile signaling?
abstract: Acrolein, a reactive aldehyde found in cigarette smoke, is thought to induce its biological effects primarily by irreversible adduction to cellular nucleophiles such as cysteine thiols. Here, we demonstrate that acrolein rapidly inactivates the seleno-enzyme thioredoxin reductase (TrxR) in human bronchiolar epithelial HBE1 cells, which recovered over 4-8h by a mechanism depending on the presence of cellular GSH and thioredoxin 1 (Trx1), and corresponding with reversal of protein-acrolein adduction. Our findings indicate that acrolein-induced protein alkylation is not necessarily a feature of irreversible protein damage, but may reflect a reversible signaling mechanism that is regulated by GSH and Trx1.
authors.affiliation: Department of Pathology, College of Medicine, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Randall
authors.forename: Milena
authors.initials: M
authors.lastname: Hristova
authors.forename: Albert
authors.initials: A
authors.lastname: van der Vliet
mesh_terms: D000171:Acrolein / Q000494:pharmacology*; D000478:Alkylation; D002460:Cell Line; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism*
chemical_list: C491203:TXN protein, human; D013879:Thioredoxins; D000171:Acrolein; D013880:Thioredoxin-Disulfide Reductase; D005978:Glutathione
keywords: Cysteine; GSH; Michael addition; Selenocysteine; Thioredoxin; Thioredoxin reductase