Possible involvement of thioredoxin reductase as well as thioredoxin in cellular sensitivity to cis-diamminedichloroplatinum (II)

Sasada, Tetsuro; Nakamura, Hajime; Ueda, Shugo; Satô, Norihito; Kitaoka, Yuki; Gon, Yasuhiro; Takabayashi, Arimichi; Spyrou, Giannis; Holmgren, Arne; Yodoi, Junji

doi:10.1016/s0891-5849(99)00101-x

Cited by 110 publications

(80 citation statements)

References 33 publications

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“…5 To examine whether modified Trx1 by acrolein or HNE inhibits TrxR1 function, we measured TrxR1 activity in a cell-free system under conditions with excess unmodified Trx1. 15 As shown in Figure 1C both acroleinand HNE-modified Trx1 significantly inhibited TrxR1 activity by 26% and 18%, respectively [TrxR1 activity, 73.9 Ϯ 3.8 (by acr-Trx1); 81.8 Ϯ 6.1 (by HNE-Trx1); 100 Ϯ 2.2 (by Trx1 control)].…”

Section: Acrolein and Hne Resulted In Thiol Modification And Inhibitementioning

confidence: 88%

Reactive Aldehyde Modification of Thioredoxin-1 Activates Early Steps of Inflammation and Cell Adhesion

Halvey

Hansen

et al. 2007

The American Journal of Pathology

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Atherosclerosis is a complex process including proinflammatory and pro-oxidative events, which recruit monocytes and lymphocytes to adhere to the surface of the injured endothelium as the first observable event. Epidemiological studies have revealed numerous risk factors for atherosclerosis including genetic and environmental risk factors, such as smoking, diet, infection, and air pollution, which interestingly have also been known to induce oxidative stress.The thioredoxin-1 (Trx1) system plays a key role in modulating redox signaling pathways regulating physiological as well as pathophysiological processes such as atherosclerosis development.1,2 Trx1 is a major substrate for thioredoxin reductase-1 (TrxR1), serving as an electron carrier to reduce peroxiredoxins, redox factor-1 (Ref1), and other proteins. A dithiol (Cys-32, Cys-35) in the active site of Trx1 undergoes reversible oxidation to the disulfide during the transfer of reducing equivalents. In addition to the redox regulatory function of the active-site cysteines (Cys-32, Cys-35), post-translational modifications of the other cysteines by oxidation (Cys-62, Cys-69), S-nitrosylation (Cys-69), and glutathionylation (Cys-73) have a significant effect on Trx1 function.3-5 Modification of thiols in Trx1 interrupts signaling mechanisms involved in cell growth, proliferation, and apoptosis. 3,4 Previous studies show that common products of lipid peroxidation, including acrolein and 4-hydroxy-2-nonenal (HNE) react with and modify functions of various cellular proteins. Acrolein and HNE are electrophilic lipids that target a number of redox-sensitive proteins, inducing multiple cellular responses through several mechanisms. 6 The cytoprotective role of acrolein and HNE in cellular mechanisms has been demonstrated at low concentrations. For example, HNE induces cytoprotective antioxidants, HO-1 and glutathione (GSH), in bovine aortic endothelial cells (BAECs) 7 and activates thioredoxin

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Section: Acrolein and Hne Resulted In Thiol Modification And Inhibitementioning

confidence: 88%

Reactive Aldehyde Modification of Thioredoxin-1 Activates Early Steps of Inflammation and Cell Adhesion

Halvey

Hansen

et al. 2007

The American Journal of Pathology

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“…Sasada et al showed that cisplatin inhibits isolated cellular TrxR with celullar enzyme activity to ~50% at a concetration of 10 µM (Sasada et al 1999).…”

Section: Cis Platinmentioning

confidence: 99%

Thioredoxin system – a novel therapeutic target

Koháryová¹,

Kollárová²

2015

gpb

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Abstract. Nowadays there are numerous pathogens that have created a resistance to commonly used antibiotics and drugs. Therefore research is focused on finding new therapeutic targets and on determination of their 3D structures that could help in designing new effective substances and inhibitors. Thioredoxin system not only plays a crucial role as thiol/disulfide redox controller, it is also essential for certain organisms as the only system ensuring the redox homeostasis. It is the redox-regulating function, which makes thioredoxin and thioredoxin reductase attractive for scientific research, especially in many studies of diseases caused by redox instability. Thanks to these facts, the proteins of thioredoxin system are suitable candidates for new therapeutic purposes. In this review we summarized the basic features of the thioredoxin system, we justified why the proteins of thioredoxin system are appropriate therapeutical targets and we provided overview of the possibilities of their inhibition by several types of inhibitors.

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“…Trx promotes cell proliferation and it is capable of increasing the growth rate and colony formation of cells (25). Trx can also increase oxidant and drug resistance of various cells (26). A variety of stress stimuli such as hypoxia and photochemical or ultra violet radiation can activate Trx (13).…”

Section: Discussionmentioning

confidence: 99%

Increased BTB-Kelch type substrate adaptor protein immunoreactivity associates with advanced stage and poor differentiation in renal cell carcinoma

Ronkainen

Vaarala²,

Kauppila³

et al. 2009

Oncol Rep

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Abstract. Renal cell carcinoma (RCC) is a malignancy with increasing incidence. Despite the well-known prognostic factors -the stage, grade and histological subtype -the clinical course of RCC can seem quite random. The aim of this study was to evaluate markers of the oxidative system as candidate prognostic factors for RCC. Our study population consisted of 152 patients who underwent operation for RCC between 1990 and 1999. The tumours were examined with three immunohistochemical markers of the oxidative system, thioredoxin (Trx), NF-E2-related factor (Nfr2) and BTBKelch type substrate adaptor protein (Keap1). Cytoplasmic Keap1 staining was related to poorer prognosis in renal cancer-specific survival. The difference was statistically significant (P=0.02). Keap1 staining was associated with a more advanced stage and a higher nuclear grade. Cytoplasmic Trx staining was associated with a trend of better prognosis in renal cancer-specific survival. Nfr2 staining was not a prognostic factor in renal cancer-specific survival. In RCC, Keap1 is associated with a more advanced disease, a higher grade and a poorer prognosis.

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Possible involvement of thioredoxin reductase as well as thioredoxin in cellular sensitivity to cis-diamminedichloroplatinum (II)

Cited by 110 publications

References 33 publications

Reactive Aldehyde Modification of Thioredoxin-1 Activates Early Steps of Inflammation and Cell Adhesion

Reactive Aldehyde Modification of Thioredoxin-1 Activates Early Steps of Inflammation and Cell Adhesion

Thioredoxin system – a novel therapeutic target

Increased BTB-Kelch type substrate adaptor protein immunoreactivity associates with advanced stage and poor differentiation in renal cell carcinoma

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