Document Detail

The effects of acrolein on peroxiredoxins, thioredoxins, and thioredoxin reductase in human bronchial epithelial cells.
MedLine Citation:
PMID:  19135121     Owner:  NLM     Status:  MEDLINE    
Inhalation is a common form of exposure to acrolein, a toxic reactive volatile aldehyde that is a ubiquitous environmental pollutant. Bronchial epithelial cells would be directly exposed to inhaled acrolein. The thioredoxin (Trx) system is essential for the maintenance of cellular thiol redox balance, and is critical for cell survival. Normally, thioredoxin reductase (TrxR) maintains the cytosolic (Trx1) and mitochondrial (Trx2) thioredoxins in the reduced state, and the thioredoxins keep the peroxiredoxins (Prx) reduced, thereby supporting their peroxidase function. The effects of acrolein on TrxR, Trx and Prx in human bronchial epithelial (BEAS-2B) cells were determined. A 30-min exposure to 5 microM acrolein oxidized both Trx1 and Trx2, although significant effects were noted for Trx1 at even lower acrolein concentrations. The effects on Trx1 and Trx2 could not be reversed by treatment with disulfide reductants. TrxR activity was inhibited 60% and >85% by 2.5 and 5 microM acrolein, respectively. The endogenous electron donor for TrxR, NADPH, could not restore its activity, and activity did not recover in cells during a 4-h acrolein-free period in complete medium. The effects of acrolein on TrxR and Trx therefore extend beyond the duration of exposure. While there was a strong correlation between TrxR inhibition and Trx1 oxidation, the irreversible effects on Trx1 suggest direct effects of acrolein rather than loss of reducing equivalents from TrxR. Trx2 did not become oxidized until > or = 90% of TrxR was inhibited, but irreversible effects on Trx2 also suggest direct effects of acrolein. Prx1 (cytosolic) and Prx3 (mitochondrial) shifted to a largely oxidized state only when >90 and 100% of their respective Trxs were oxidized. Prx oxidation was readily reversed with a disulfide reductant, suggesting that Prx oxidation resulted from lack of reducing equivalents from Trx and not direct reaction with acrolein. The effects of acrolein on the thioredoxin system and peroxiredoxins could have important implications for cell survival, redox-sensitive cell signaling, and tolerance to other oxidant insults.
Charles R Myers; Judith M Myers
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-12-24
Journal Detail:
Title:  Toxicology     Volume:  257     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-02-02     Completed Date:  2009-03-20     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  95-104     Citation Subset:  IM    
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
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MeSH Terms
Acrolein / toxicity*
Air Pollutants / toxicity*
Bronchi / drug effects*,  enzymology
Cells, Cultured
Disulfides / metabolism
Dose-Response Relationship, Drug
Enzyme Inhibitors / toxicity*
Epithelial Cells / drug effects*,  enzymology
Mitochondrial Proteins / metabolism
Peroxiredoxin III
Peroxiredoxins / metabolism*
Thioredoxin-Disulfide Reductase / antagonists & inhibitors*,  metabolism
Thioredoxins / metabolism*
Grant Support
ES012707/ES/NIEHS NIH HHS; R01 ES012707-01/ES/NIEHS NIH HHS; R01 ES012707-02/ES/NIEHS NIH HHS; R01 ES012707-03/ES/NIEHS NIH HHS; R01 ES012707-04/ES/NIEHS NIH HHS
Reg. No./Substance:
0/Air Pollutants; 0/Disulfides; 0/Enzyme Inhibitors; 0/Mitochondrial Proteins; 0/TXN2 protein, human; 107-02-8/Acrolein; 52500-60-4/Thioredoxins; EC protein, human; EC protein, human; EC III; EC; EC Reductase

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