Effect of acrolein and glutathione depleting agents on thioredoxin

Toxicology
Xianmei YangJames P Kehrer

Abstract

Acrolein is a widespread environmental pollutant that reacts rapidly with nucleophiles, especially cellular thiols. In addition to glutathione (GSH), thioredoxin (Trx) and thioredoxin reductase (TR) contain thiol groups and may react with electrophiles. In the present study, A549 cells treated with 5-25 microM acrolein for 30 min lost cellular Trx activity in a dose-dependent fashion. Over 90% of Trx activity was lost at concentrations of 25 microM or greater. In contrast, Trx protein content, as assessed by western blotting, was not altered immediately after the 30 min acrolein treatment. Both Trx activity and protein levels increased 4h after the acrolein treatment. However, Trx activity remained below control levels at 24h. A similar dose-response relationship was seen with TR in A549 cells exposed to acrolein. There was, however, a rapid recovery of TR activity such that it attained normal levels by 4h after doses < or = 75 microM acrolein. Diethyl maleate (DEM), a common but not highly specific, agent used to deplete GSH, also inactivated Trx. A 2 h exposure of A549 cells to 1 mM DEM depleted cellular GSH by ~50% and diminished Trx activity by over 67%. Lower DEM doses (0.125 mM and 0.25 mM) for 1h had no significant effec...Continue Reading

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Citations

Apr 16, 2010·Canadian Journal of Physiology and Pharmacology·Julie RoyDiana A Averill-Bates
May 2, 2008·Chemical Research in Toxicology·Yan ChenDean P Jones
Jun 14, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Min HeDean P Jones
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Nov 24, 2020·Frontiers in Physiology·Tanner J Wetzel, Todd A Wyatt

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