The effects of hexavalent chromium on thioredoxin reductase and peroxiredoxins in human bronchial epithelial cells.
Inhalational exposure to hexavalent chromium (Cr(VI)) compounds (e.g., chromates) is of concern in many Cr-related industries and their surrounding environments. The bronchial epithelium is directly exposed to inhaled Cr(VI). Cr(VI) species gain easy access inside cells, where they are reduced to reactive Cr species, which may also contribute to the generation of reactive oxygen species. The thioredoxin (Trx) system promotes cell survival and has a major role in maintaining intracellular thiol redox balance. Previous studies with normal human bronchial epithelial cells (BEAS-2B) demonstrated that chromates cause dose- and time-dependent oxidation of Trx1 and Trx2. The Trx's keep many intracellular proteins reduced, including the peroxiredoxins (Prx's). Prx1 (cytosolic) and Prx3 (mitochondrial) were oxidized by Cr(VI) treatments that oxidized all, or nearly all, of the respective Trx's. Prx oxidation is therefore probably the result of a lack of reducing equivalents from Trx. Trx reductases (TrxR's) keep the Trx's largely in the reduced state. Cr(VI) caused pronounced inhibition of TrxR, but the levels of TrxR protein remained unchanged. The inhibition of TrxR was not reversed by removal of residual Cr(VI) or by NADPH, the endogenous electron donor for TrxR. In contrast, the oxidation of Trx1, Trx2, and Prx3 was reversible by disulfide reductants. Prolonged inhibition of TrxR in Cr(VI)-treated cells might contribute to the sustained oxidation of Trx's and Prx's. Reduced Trx binds to an N-terminal domain of apoptosis signaling kinase (ASK1), keeping ASK1 inactive. Cr(VI) treatments that significantly oxidized Trx1 resulted in pronounced dissociation of Trx1 from ASK1. Overall, the effects of Cr(VI) on the redox state and function of the Trx's, Prx's, and TrxR in the bronchial epithelium could have important implications for redox-sensitive cell signaling and tolerance of oxidant insults.
Myers
Judith M
JM
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Myers
Charles R
CR
D001980:Bronchi / Q000187:drug effects* / Q000201:enzymology; D002478:Cells, Cultured; D002857:Chromium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D002857:Chromium; C074702:chromium hexavalent ion; D054464:Peroxiredoxins; D013880:Thioredoxin-Disulfide Reductase
Biochem J. 2005 Mar 1;386(Pt 2):215-9
15647005
Biochem Biophys Res Commun. 2008 Apr 11;368(3):832-6
18267104
Chem Res Toxicol. 2001 Sep;14(9):1315-22
11559048
Biochim Biophys Acta. 1994 Apr 12;1226(1):65-72
8155741
Eur J Biochem. 2000 Oct;267(20):6102-9
11012661
Biol Trace Elem Res. 1995 Dec;50(3):175-80
8962789
Biochem Pharmacol. 1984 May 15;33(10):1661-70
6233980
Science. 1997 Jan 3;275(5296):90-4
8974401
J Biol Chem. 1998 Aug 7;273(32):20096-101
9685351
Br J Cancer. 1994 Jul;70(1):160-6
8018529
J Cell Physiol. 2002 Apr;191(1):95-104
11920685
Xenobiotica. 1985 Aug-Sep;15(8-9):735-41
4072261
Free Radic Biol Med. 2007 Mar 15;42(6):738-55; discussion 735-7
17320757
Annu Rev Pharmacol Toxicol. 2006;46:215-34
16402904
Mutat Res. 1992 Jan;278(1):69-79
1370121
Free Radic Biol Med. 2008 Mar 15;44(6):1001-9
18164270
PLoS One. 2008 Apr 02;3(4):e1846
18382651
Chem Res Toxicol. 1991 Nov-Dec;4(6):616-25
1807444
Arch Toxicol. 1990;64(3):169-76
2372230
Int Arch Occup Environ Health. 1995;67(3):147-52
7591171
J Biol Chem. 1998 May 1;273(18):10835-42
9556556
J Bacteriol. 1997 Feb;179(4):1143-52
9023196
J Inorg Biochem. 1999 May 30;75(1):37-44
10402675
Br J Ind Med. 1991 Oct;48(10):675-83
1931726
EMBO J. 1998 May 1;17(9):2596-606
9564042
J Biol Chem. 2007 Apr 20;282(16):11885-92
17329258
Carcinogenesis. 1984 Sep;5(9):1207-9
6467509
Toxicology. 2008 Apr 18;246(2-3):222-33
18328613
Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9533-8
11481439
J Biol Chem. 2004 Oct 1;279(40):41975-84
15280382
Annu Rev Biochem. 1985;54:237-71
3896121
Carcinogenesis. 1986 May;7(5):831-5
3698209
Mol Cell Biol. 2003 Feb;23(3):916-22
12529397
J Inorg Biochem. 1999 Nov-Dec;77(3-4):177-83
10643657
Free Radic Biol Med. 2006 Jan 1;40(1):138-45
16337887
Anal Biochem. 2005 Mar 15;338(2):216-23
15745741
Chem Biol Interact. 1979 Aug;26(3):267-80
509690
J Inorg Biochem. 2008 Jul;102(7):1449-62
18279960
Scand J Work Environ Health. 1983 Jun;9(3):247-52
6612265
Cancer Res. 2008 Oct 15;68(20):8269-77
18922898
J Toxicol Environ Health B Crit Rev. 1999 Jan-Mar;2(1):87-104
10081526
Scand J Work Environ Health. 1993;19 Suppl 1:81-9
8159981
Cancer Res. 1983 Dec;43(12 Pt 1):5662-7
6640521
Cancer Res. 1994 May 1;54(9):2342-6
8162579
Annu Rev Biophys Biomol Struct. 2001;30:421-55
11441809
Environ Health Perspect. 1996 Oct;104 Suppl 5:917-9
8933034
Biochem Pharmacol. 2008 Oct 30;76(9):1097-109
18789312
J Biol Chem. 2003 Aug 29;278(35):33408-15
12816947
J Biol Chem. 1977 Jul 10;252(13):4600-6
17603
Free Radic Biol Med. 2001 Dec 1;31(11):1287-312
11728801
Trends Biotechnol. 1993 Aug;11(8):353-9
7764182
Am J Physiol Gastrointest Liver Physiol. 2002 Dec;283(6):G1352-9
12433666
Toxicology. 2008 Jan 14;243(1-2):164-76
18023956
Chem Res Toxicol. 1998 Feb;11(2):119-29
9511903
Environ Health Perspect. 1998 Aug;106 Suppl 4:969-74
9703480
Anal Biochem. 1999 Aug 15;273(1):73-80
10452801
FEBS Lett. 2006 Dec 11;580(28-29):6596-602
17113580
Arch Environ Health. 1983 May-Jun;38(3):148-55
6347098
Angew Chem Int Ed Engl. 2003 Oct 13;42(39):4742-58
14562341
Arch Biochem Biophys. 1992 Jan;292(1):323-7
1309299
J Biol Chem. 1995 Feb 24;270(8):3479-82
7876079
J Biol Chem. 2008 Apr 11;283(15):9986-98
18250162
Chem Biol Interact. 1989;69(2-3):175-92
2495190
Int Arch Occup Environ Health. 1993;65(1 Suppl):S197-200
8406925
J Inorg Biochem. 1990 Sep;40(1):1-12
2178178
Carcinogenesis. 1992 Aug;13(8):1319-24
1499083