Faculty Collaboration Database

The effects of acrolein on the thioredoxin system: implications for redox-sensitive signaling. Mol Nutr Food Res 2011 Sep;55(9):1361-74

Date

08/04/2011

Pubmed ID

21812108

Pubmed Central ID

PMC3517082

DOI

10.1002/mnfr.201100224

Scopus ID

2-s2.0-80052524789 (requires institutional sign-in at Scopus site)   26 Citations

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.

Author List

Myers CR, Myers JM, Kufahl TD, Forbes R, Szadkowski A

Author

Adam O. Szadkowski MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acrolein
Endothelium, Vascular
Enzyme Inhibitors
Humans
MAP Kinase Kinase Kinase 5
Peroxiredoxins
Selenocysteine
Signal Transduction
Sulfhydryl Compounds
Thioredoxin-Disulfide Reductase
Thioredoxins
p38 Mitogen-Activated Protein Kinases