US EPA

1577026 

Journal Article 

Abstract 

The effects of hexavalent chromium on thioredoxin reductase and peroxiredoxins in human bronchial epithelial cells 

Myers, JM; Antholine, WE; Myers, CR 

2008 

Yes 

Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 

45 

Suppl. 

S73-S74 

English 

WOS:000260867900206 

http://www.sciencedirect.com/science/article/pii/S0891584908006242
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is part of a larger document 3452652 SFRBM's 15th Annual Meeting: Program and Abstracts

Cr(VI) (hexavalent chromium) is cytotoxic and carcinogenic, and bronchial epithelial cells are directly exposed to inhaled Cr(VI). Redox stress can result from intracellular Cr(VI) reduction which generates reactive Cr species and ROS (e.g. hydroxyl radical). The thioredoxin (Trx) system is important for the maintenance of cellular thiol redox status. Cr(VI) treatment of normal human bronchial epithelial cells (BEAS-2B) results in the oxidation of Trx1 (cytosolic) and Trx2 (mitochondrial). Peroxiredoxins (Prx) are ubiquitous peroxidases that are kept in the reduced/active state by the Trxs. Prx1 (cytosolic) and Prx3 (mitochondrial) in cells were oxidized by Cr(VI) treatments that oxidized all, or nearly all, of the respective Trxs. Prx oxidation may therefore reflect the functional state of the Trx isoforms. Trx reductases (TrxR) maintain the Trxs largely in the reduced state. Cr(VI) caused pronounced inhibition of TrxR, but the levels of TrxR protein remained unchanged. Direct redox interactions between purified TrxR1 and Cr(VI) were observed in vitro by ESR. While diversion of electrons to Cr(VI) might impair Trx reduction in cells, the effects on TrxR were prolonged — they were not reversed by removal of residual Cr(VI) or by NADPH, the endogenous electron donor for TrxR. in contrast, the oxidation of Trx1 was reversible by a disulfide reductant. Prolonged inhibition of TrxR in Cr(VI)-treated cells could contribute to the oxidation of Trxs and Prxs in cells. in unstressed cells, reduced Trx binds to an N-terminal domain of apoptosis signaling kinase (ASK1), keeping ASK1 inactive. Cr(VI) treatments that significantly oxidized Trx1 in BEAS-2B cells resulted in pronounced dissociation of Trx1 from ASK1. This could facilitate ASK1 activation and therefore downstream MAP kinases that have effects on multiple transcription factors and events that effect cell growth vs. apoptosis. Overall, the effects of Cr(VI) on the redox state and function of the Trxs, Prxs, and TrxR in the bronchial epithelium could have important implications for redox-sensitive cell signaling and tolerance to oxidant insults. 

Society for Free Radical Biology and Medicine 15th Annual Meeting 

Indianapolis, IN 

November 19-23, 2008