Faculty Collaboration Database

The effects of chromium(VI) on the thioredoxin system: implications for redox regulation. Free Radic Biol Med 2012 May 15;52(10):2091-107

Date

05/01/2012

Pubmed ID

22542445

Pubmed Central ID

PMC3955998

DOI

10.1016/j.freeradbiomed.2012.03.013

Scopus ID

2-s2.0-84861058076 (requires institutional sign-in at Scopus site)   62 Citations

Abstract

Hexavalent chromium [Cr(VI)] compounds are highly redox active and have long been recognized as potent cytotoxins and carcinogens. The intracellular reduction of Cr(VI) generates reactive Cr intermediates, which are themselves strong oxidants, as well as superoxide, hydrogen peroxide, and hydroxyl radical. These probably contribute to the oxidative damage and effects on redox-sensitive transcription factors that have been reported. However, the identification of events that initiate these signaling changes has been elusive. More recent studies show that Cr(VI) causes irreversible inhibition of thioredoxin reductase (TrxR) and oxidation of thioredoxin (Trx) and peroxiredoxin (Prx). Mitochondrial Trx2/Prx3 are more sensitive to Cr(VI) treatment than cytosolic Trx1/Prx1, although both compartments show thiol oxidation with higher doses or longer treatments. Thiol redox proteomics demonstrate that Trx2, Prx3, and Trx1 are among the most sensitive proteins in cells to Cr(VI) treatment. Their oxidation could therefore represent initiating events that have widespread implications for protein thiol redox control and for multiple aspects of redox signaling. This review summarizes the effects of Cr(VI) on the TrxR/Trx system and how these events could influence a number of downstream redox signaling systems that are influenced by Cr(VI) exposure. Some of the signaling events discussed include the activation of apoptosis signal regulating kinase and MAP kinases (p38 and JNK) and the modulation of a number of redox-sensitive transcription factors including AP-1, NF-κB, p53, and Nrf2.

Author List

Myers CR

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

Animals
Chromium
Humans
Mice
Mitochondria
Mitogen-Activated Protein Kinases
NF-E2-Related Factor 2
NF-kappa B
Oxidation-Reduction
Oxidative Stress
Peroxiredoxins
Thioredoxin-Disulfide Reductase
Thioredoxins
Transcription Factor AP-1
Tumor Suppressor Protein p53