The intracellular redox stress caused by hexavalent chromium is selective for proteins that have key roles in cell survival and thiol redox control. Toxicology 2011 Mar 15;281(1-3):37-47
Date
01/18/2011Pubmed ID
21237240Pubmed Central ID
PMC3039098DOI
10.1016/j.tox.2011.01.001Scopus ID
2-s2.0-79851516124 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
Hexavalent chromium [Cr(VI)] compounds (e.g. chromates) are strong oxidants that readily enter cells where they are reduced to reactive Cr intermediates that can directly oxidize some cell components and can promote the generation of reactive oxygen and nitrogen species. Inhalation is a major route of exposure which directly exposes the bronchial epithelium. Previous studies with non-cancerous human bronchial epithelial cells (BEAS-2B) demonstrated that Cr(VI) treatment results in the irreversible inhibition of thioredoxin reductase (TrxR) and the oxidation of thioredoxins (Trx) and peroxiredoxins (Prx). The mitochondrial Trx/Prx system is somewhat more sensitive to Cr(VI) than the cytosolic Trx/Prx system, and other redox-sensitive mitochondrial functions are subsequently affected including electron transport complexes I and II. Studies reported here show that Cr(VI) does not cause indiscriminant thiol oxidation, and that the Trx/Prx system is among the most sensitive of cellular protein thiols. Trx/Prx oxidation is not unique to BEAS-2B cells, as it was also observed in primary human bronchial epithelial cells. Increasing the intracellular levels of ascorbate, an endogenous Cr(VI) reductant, did not alter the effects on TrxR, Trx, or Prx. The peroxynitrite scavenger MnTBAP did not protect TrxR, Trx, Prx, or the electron transport chain from the effects of Cr(VI), implying that peroxynitrite is not required for these effects. Nitration of tyrosine residues of TrxR was not observed following Cr(VI) treatment, further ruling out peroxynitrite as a significant contributor to the irreversible inhibition of TrxR. Cr(VI) treatments that disrupt the TrxR/Trx/Prx system did not cause detectable mitochondrial DNA damage. Overall, the redox stress that results from Cr(VI) exposure shows selectivity for key proteins which are known to be important for redox signaling, antioxidant defense, and cell survival.
Author List
Myers JM, Antholine WE, Myers CRMESH terms used to index this publication - Major topics in bold
Ascorbic AcidBronchi
Cell Line
Cell Survival
Chromium
DNA Damage
DNA, Mitochondrial
Electron Spin Resonance Spectroscopy
Electrophoresis, Gel, Two-Dimensional
Humans
Oxidation-Reduction
Oxidative Stress
Peroxiredoxins
Respiratory Mucosa
Thioredoxins