Expression of the thioredoxin-thioredoxin reductase system in the inflamed joints of patients with rheumatoid arthritis

Maurice, Madelon M.; Nakamura, Hajime; Gringhuis, Sonja I.; Okamoto, Takashi; Yoshida, Shigeaki; Kullmann, Frank; Lechner, Sandra; Voort, E. A. M. Van Der; Leow, Angela; Versendaal, Johannes; Müller‐Ladner, Ulf; Yodoi, Junji; Tak, Paul P.; Breedveld, Ferdinand C.; Verweij, Cornelis L.

doi:10.1002/1529-0131(199911)42:11<2430::aid-anr22>3.0.co;2-6

Cited by 109 publications

(52 citation statements)

References 44 publications

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“…Indeed, increased TF + MP levels correlate with hypercoagulability in endotoxemic mice (79), and extracellular TRX levels are significantly elevated in plasma of sepsis patients (80). Similarly, P2RX7 signaling is implicated in rheumatoid arthritis (81), and high levels of extracellular TRX (82,83) as well as of TF + MPs (84) are detected in the synovial fluids of patients. Notably, the TRXR inhibitor auranofin is efficacious in the treatment of rheumatoid arthritis.…”

Section: Discussionmentioning

confidence: 99%

Caspase-1–mediated pathway promotes generation of thromboinflammatory microparticles

Rothmeier¹,

Marchese²,

Petrich³

et al. 2015

J. Clin. Invest.

104

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Section: Discussionmentioning

confidence: 99%

Caspase-1–mediated pathway promotes generation of thromboinflammatory microparticles

Rothmeier¹,

Marchese²,

Petrich³

et al. 2015

J. Clin. Invest.

104

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“…In addition, TrxR is involved in the redox activity of RAW264.7 macrophages [54][55][56]. Our interest in examining the binding of gold complexes, and possibly Au NPs, to TrxR was derived in part from the contribution that these interactions may make to their anti-arthritic activity [18,19].…”

Section: Thioredoxin Reductase Binding Studiesmentioning

confidence: 99%

“…Both Trx and TrxR are over-expressed in synovial cells or fluid of RA patients [18,19]. Inhibition of TrxR by gold drugs has attracted interest due to the presence of a selenocysteine residue at its active site, and the greater affinity of Au(I) for selenol groups compared to thiols [20,21].…”

Section: Introductionmentioning

confidence: 99%

An investigation into the interactions of gold nanoparticles and anti-arthritic drugs with macrophages, and their reactivity towards thioredoxin reductase

James

Sluyter

et al. 2015

Journal of Inorganic Biochemistry

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“…Another important antioxidant system that would suffer from TrxR inhibition is that of the mammalian peroxiredoxins, which all require functional Trx for regeneration (16). Furthermore, cytokine functions of extracellular Trx, as well as increased Trx and TrxR levels in some tumor cell lines and in synovial fluid or tissue of patients suffering from rheumatoid arthritis (10,17), argue for targeting of TrxR as a possible therapeutic approach in certain diseases. In fact, TrxR is inactivated by several compounds in clinical use, including 1,3-bis-(2-chloro-ethyl)-1-nitrosourea (BCNU) (18), anticancer platinum compounds (19), antiarthritic gold compounds (20,21), and immunostimulatory dinitrohalobenzenes (22).…”

mentioning

confidence: 99%

Interactions of Quinones with Thioredoxin Reductase

Čėnas¹,

Nivinskas²,

Anusevičius³

et al. 2004

Journal of Biological Chemistry

124

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Mammalian thioredoxin reductases (TrxR) are important selenium-dependent antioxidant enzymes. Quinones, a wide group of natural substances, human drugs, and environmental pollutants may act either as TrxR substrates or inhibitors. Here we systematically analyzed the interactions of TrxR with different classes of quinone compounds. We found that TrxR catalyzed mixed single-and two-electron reduction of quinones, involving both the selenium-containing motif and a second redox center, presumably FAD. Compared with other related pyridine nucleotide-disulfide oxidoreductases such as glutathione reductase or trypanothione reductase, the k cat /K m value for quinone reduction by TrxR was about 1 order of magnitude higher, and it was not directly related to the one-electron reduction potential of the quinones. A number of quinones were reduced about as efficiently as the natural substrate thioredoxin. We show that TrxR mainly cycles between the four-electron reduced (EH 4 ) and two-electron reduced (EH 2 ) states in quinone reduction. The redox potential of the EH 2 /EH 4 couple of TrxR calculated according to the Haldane relationship with NADPH/NADP ؉ was ؊0.294 V at pH 7.0. Antitumor aziridinylbenzoquinones and daunorubicin were poor substrates and almost inactive as reversible TrxR inhibitors. However, phenanthrene quinone was a potent inhibitor (approximate K i ‫؍‬ 6.3 ؎ 1 M). As with other flavoenzymes, quinones could confer superoxide-producing NADPH oxidase activity to mammalian TrxR. A unique feature of this enzyme was, however, the fact that upon selenocysteine-targeted covalent modification, which inactivates its normal activity, reduction of some quinones was not affected, whereas that of others was severely impaired. We conclude that interactions with TrxR may play a considerable role in the complex mechanisms underlying the diverse biological effects of quinones.Thioredoxin reductase (TrxR, 1 EC 1.8.1.9) catalyzes NADPHdependent reduction of the redox-active disulfide in thioredoxin (Trx), which serves a wide range of functions in cellular proliferation and redox control (1, 2). Thioredoxin reductases are homodimeric proteins that differ in properties between different classes of organisms. Low M r (34-kDa subunit) TrxRs of prokaryotes, plants, or yeast contain FAD and a redox-active disulfide/dithiol active site and display narrow substrate specificities. High M r (54 -58 kDa) TrxRs of animals have in contrast remarkably wide substrate specificities, explained by an additional easily accessible C-terminal redox center. This redox center is either a disulfide/dithiol as in TrxR of Plasmodium falciparum or Drosophila melanogaster or a selenocysteinecontaining selenenylsulfide/selenolthiol motif as found in TrxRs of mammals (3-6). In recent years, the catalytic mechanism of mammalian TrxR has been unraveled in significant detail. The three-dimensional crystal structure of rat TrxR is similar to that of glutathione reductase, including conserved FAD and NADP(H)-binding domains, but TrxR has a 16-residue C-term...

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Expression of the thioredoxin-thioredoxin reductase system in the inflamed joints of patients with rheumatoid arthritis

Cited by 109 publications

References 44 publications

Caspase-1–mediated pathway promotes generation of thromboinflammatory microparticles

Caspase-1–mediated pathway promotes generation of thromboinflammatory microparticles

An investigation into the interactions of gold nanoparticles and anti-arthritic drugs with macrophages, and their reactivity towards thioredoxin reductase

Interactions of Quinones with Thioredoxin Reductase

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