Faculty Collaboration Database

Acrolein oxidizes the cytosolic and mitochondrial thioredoxins in human endothelial cells. Toxicology 2008 Jan 14;243(1-2):164-76

Date

11/21/2007

Pubmed ID

18023956

Pubmed Central ID

PMC2220080

DOI

10.1016/j.tox.2007.10.004

Scopus ID

2-s2.0-37049031908 (requires institutional sign-in at Scopus site)   24 Citations

Abstract

Acrolein is a reactive aldehyde that is a widespread environmental pollutant and can be generated endogenously from lipid peroxidation. The thioredoxin (Trx) system in endothelial cells plays a major role in the maintenance of cellular thiol redox balance, and is critical for cell survival. Normally, cells maintain the cytosolic (Trx1) and mitochondrial (Trx2) thioredoxins largely in the reduced state. In human microvascular endothelial cells, Trx1 was more sensitive than Trx2 to oxidation by acrolein. A 30-min exposure to 2.5 microM acrolein caused partial oxidation of Trx1 but not Trx2. The active site dithiol of Trx1 was essentially completely oxidized by 5 microM acrolein whereas 12.5 microM was required for complete oxidation of Trx2. Partial recovery of the Trx1 redox status was observed over a 4h acrolein-free recovery period, with increases in the reduced form and decreases in the fully oxidized form. For cells treated with 2.5 or 5 microM acrolein the recovery did not require protein synthesis, whereas protein synthesis was required for the return of reduced Trx1 in cells treated with 12.5 microM acrolein. Pretreatment of cells with N-acetylcysteine (NAC) resulted in partial protection of Trx1 from oxidation by acrolein. In cells treated with acrolein for 30 min, followed by a 14- to 16-h acrolein-free period, small but significant cytotoxic effects were observed with 2.5 microM acrolein whereas all cells were adversely affected by >or= 12.5 microM. NAC pretreatment significantly decreased the percentage of stressed cells subsequently exposed to 5 or 12.5 microM acrolein. Given the critical role of the thioredoxins in cell survival, the ability of acrolein to oxidize both thioredoxins should be taken into account for a thorough understanding of its cytotoxic effects.

Author List

Szadkowski A, Myers CR

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

Acetylcysteine
Acrolein
Cell Line
Cytosol
Endothelial Cells
Endothelium, Vascular
Environmental Pollutants
Humans
Mitochondria
Oxidation-Reduction
Thioredoxins