Merck
  • Home
  • Search Results
  • The conserved Trp114 residue of thioredoxin reductase 1 has a redox sensor-like function triggering oligomerization and crosslinking upon oxidative stress related to cell death.

The conserved Trp114 residue of thioredoxin reductase 1 has a redox sensor-like function triggering oligomerization and crosslinking upon oxidative stress related to cell death.

Cell death & disease (2015-01-23)
J Xu, S E Eriksson, M Cebula, T Sandalova, E Hedström, I Pader, Q Cheng, C R Myers, W E Antholine, P Nagy, U Hellman, G Selivanova, Y Lindqvist, E S J Arnér
ABSTRACT

The selenoprotein thioredoxin reductase 1 (TrxR1) has several key roles in cellular redox systems and reductive pathways. Here we discovered that an evolutionarily conserved and surface-exposed tryptophan residue of the enzyme (Trp114) is excessively reactive to oxidation and exerts regulatory functions. The results indicate that it serves as an electron relay communicating with the FAD moiety of the enzyme, and, when oxidized, it facilitates oligomerization of TrxR1 into tetramers and higher multimers of dimers. A covalent link can also be formed between two oxidized Trp114 residues of two subunits from two separate TrxR1 dimers, as found both in cell extracts and in a crystal structure of tetrameric TrxR1. Formation of covalently linked TrxR1 subunits became exaggerated in cells on treatment with the pro-oxidant p53-reactivating anticancer compound RITA, in direct correlation with triggering of a cell death that could be prevented by antioxidant treatment. These results collectively suggest that Trp114 of TrxR1 serves a function reminiscent of an irreversible sensor for excessive oxidation, thereby presenting a previously unrecognized level of regulation of TrxR1 function in relation to cellular redox state and cell death induction.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
BIS-TRIS, BioPerformance Certified, suitable for cell culture, suitable for insect cell culture, ≥98.0%
Sigma-Aldrich
BIS-TRIS, BioXtra, ≥98.0% (titration)
Sigma-Aldrich
BIS-TRIS, ≥98.0% (titration)
Sigma-Aldrich
DL-Tryptophan, ≥99% (HPLC)
Sigma-Aldrich
DL-Tryptophan, ≥99% (HPLC)
Sigma-Aldrich
BIS-TRIS, BioUltra, ≥99.0% (NT)
Sigma-Aldrich
Acetonitrile solution, contains 0.05 % (v/v) trifluoroacetic acid
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)
SAFC
BIS-TRIS
Supelco
Residual Solvent - Acetonitrile, Pharmaceutical Secondary Standard; Certified Reference Material
SAFC
BIS-TRIS
Tryptophan, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Hexylene glycol, BioXtra, ≥99% (GC)
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Sigma-Aldrich
Phenylacetic acid, suitable for plant cell culture
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Sigma-Aldrich
Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
Sigma-Aldrich
α-Cyano-4-hydroxycinnamic acid, ≥98% (TLC), powder
Sigma-Aldrich
α-Cyano-4-hydroxycinnamic acid, 97%
Sigma-Aldrich
1,6-Hexanediol, 99%
Sigma-Aldrich
Phenylacetic acid, ≥99%, FCC, FG
Sigma-Aldrich
Phenylacetic acid, 99%
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.6%, ReagentPlus®
Sigma-Aldrich
1,6-Hexanediol, 97%
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Acetonitrile, anhydrous, 99.8%
Sigma-Aldrich
α-Cyano-4-hydroxycinnamic acid, 99%
Sigma-Aldrich
8-Octanoyloxypyrene-1,3,6-trisulfonic acid trisodium salt, suitable for fluorescence, ≥90% (HPCE)