Hexavalent chromium causes the oxidation of thioredoxin in human bronchial epithelial cells

Abstract

Hexavalent chromium [Cr(VI)] species such as chromates are cytotoxic. Inhalational exposure is a primary concern in many Cr-related industries and their immediate environments, and bronchial epithelial cells are directly exposed to inhaled Cr(VI). Chromates are readily taken up by cells and are reduced to reactive Cr species which may also result in the generation of reactive oxygen species (ROS). The thioredoxin (Trx) system has a key role in the maintenance of cellular thiol redox balance and is essential for cell survival. Cells normally maintain the cytosolic (Trx1) and mitochondrial (Trx2) thioredoxins largely in the reduced state. Redox western blots were used to assess the redox status of the thioredoxins in normal human bronchial epithelial cells (BEAS-2B) incubated with soluble Na 2 CrO 4 or insoluble ZnCrO 4 for different periods of time. Both chromates caused a doseand time-dependent oxidation of Trx2 and Trx1. Trx2 was more susceptible in that it could all be converted to the oxidized form, whereas a small amount of reduced Trx1 remained even after prolonged treatment with higher Cr concentrations. Only one of the dithiols, presumably the active site, of Trx1 was oxidized by Cr(VI). Cr(VI) did not cause significant GSH depletion or oxidation indicating that Trx oxidation does not result from a general oxidation of cellular thiols. With purified Trx and thioredoxin reductase (TrxR) in vitro, Cr(VI) also resulted in Trx oxidation. It was determined that purified TrxR has pronounced Cr(VI) reducing activity, so competition for electron flow from TrxR might impair its ability to reduce Trx. The in vitro data also suggested some direct redox interaction between Cr(VI) and Trx. The ability of Cr(VI) to cause Trx oxidation in cells could contribute to its cytotoxic effects, and could have important implications for cell survival, redoxsensitive cell signaling, and the cells' tolerance of other oxidant insults.

Effects of temperature and chromium (III) ion on the structure of bovine b-Lactoglobulin-A

“…12 Trace elements, including the essential and the toxic, play an important role in the life and environmental sciences; one of them is chromium (Cr). 13 Chromium is an important transition metal ion with diverse industrial applications and is an essential micronutrient required to promote the action of insulin in body tissues so that the body can use sugars, proteins and fats. 14 Two of the most important oxidation states of chromium are Cr (III) and Cr (VI).…”

“…Cr 6+ has been shown to be carcinogenic and mutagenic to biological system. 13,14 On the contrary, Cr 3+ salts such as chromium polynicotinate, chromium chloride and chromium picolinate are used as micronutrients and nutritional supplements and have been demonstrated to exhibit a significant number of health benefits in animals and human. 16 The Cr deficiency includes symptoms resembling diabetes, such as glucose intolerance impairment with the requirement of increasing insulin, etc, and Cr supplement can alleviate these symptoms.…”

“…However, up to now, the biological function of Cr in an organism is still unclear and the concentration of Cr in many biological materials is usually at an ultra trace level. 13 The epidemiological studies show that the Cr 6+ causes increased risk of bone, prostate, lymphomas, Hodgkin's, leukemia, stomach, genital, renal, and bladder cancer, reflecting the ability of Cr 6+ to penetrate all tissues in the body. 17 However, 16 Cr 3+ complexes in proper ligand environment have been shown to induce chromosomal aberrations, mutagenicity in Salmonella bacteria (S. typhimurium), cytotoxicity and genotoxicity in cell lines.…”

“…17 Direct effects on protein and DNA have been shown in terms of DNA-protein cross-linking, DNA scission, plasmid cleavage and protein cleavage. [13][14][15][16][17] The relative importance of the chromium ions and of the free oxidizing radicals that may generate in causing cancers and allergic sensitization remain to be elucidated. Our previous studies showed that Cr 3+ could bind to BLG-A, and the number of binding sites for the metal ion on BGL-A and the binding strength have been reported.…”

Liver Aspartate Transaminase Isoenzymes as Biomarkers of Chronic Exposure to Chromium(VI)

“…In many occupations, workers handling chromium(VI)-containing products are at the risk of lung cancer, dermatitis, and gastrointestinal ulcers (1,2). Hexavalent chromium is transported into the cell via non-specifi c anion transport systems (3,4), where it converts to trivalent chromium (Cr III ), whose highest levels have been reported in the kidney, liver, spleen, and bones (5). Although cytotoxic mechanisms are not exactly understood, several studies have showed that Cr VI induces oxidative stress, DNA damage, single-and double-strand breaks, and affects survival signalling pathways (6)(7)(8).…”