title: The effects of acrolein on the thioredoxin system: implications for redox-sensitive signaling.
abstract: The reactive aldehyde acrolein is a ubiquitous environmental pollutant and is also generated endogenously. It is a strong electrophile and reacts rapidly with nucleophiles including thiolates. This review focuses on the effects of acrolein on thioredoxin reductase (TrxR) and thioredoxin (Trx), which are major regulators of intracellular protein thiol redox balance. Acrolein causes irreversible effects on TrxR and Trx, which are consistent with the formation of covalent adducts to selenocysteine and cysteine residues that are key to their activity. TrxR and Trx are more sensitive than some other redox-sensitive proteins, and their prolonged inhibition could disrupt a number of redox-sensitive functions in cells. Among these effects are the oxidation of peroxiredoxins and the activation of apoptosis signal regulating kinase (ASK1). ASK1 promotes MAP kinase activation, and p38 activation contributes to apoptosis and a number of other acrolein-induced stress responses. Overall, the disruption of the TrxR/Trx system by acrolein could be significant early and prolonged events that affect many aspects of redox-sensitive signaling and oxidant stress.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. cmyers@mcw.edu
authors.forename: Charles R
authors.initials: CR
authors.lastname: Myers
authors.forename: Judith M
authors.initials: JM
authors.lastname: Myers
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Kufahl
authors.forename: Rachel
authors.initials: R
authors.lastname: Forbes
authors.forename: Adam
authors.initials: A
authors.lastname: Szadkowski
mesh_terms: D000171:Acrolein / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity; D006801:Humans; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D054464:Peroxiredoxins / Q000378:metabolism; D017279:Selenocysteine / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D013438:Sulfhydryl Compounds; D017279:Selenocysteine; D013879:Thioredoxins; D000171:Acrolein; D054464:Peroxiredoxins; D013880:Thioredoxin-Disulfide Reductase; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5