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1328192 
Journal Article 
Review 
Reactive oxygen species, antioxidants, and the mammalian thioredoxin system: This review is based on the licentiate thesis: Thioredoxin reductase—interactions with the redox active compounds 1-chloro-2,4-dinitrobenzene and lipoic acid” by Jonas Nordberg, 2001, Karolinska Institute, Stockholm, ISBN 91-631-1064-4 
Nordberg, J; Arnér, ESJ 
2001 
Yes 
Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 
31 
11 
1287-1312 
English 
11728801 
WOS:000172597400001 
Reactive oxygen species (ROS) are known mediators of
intracellular signaling cascades. Excessive production of ROS may, however, lead to oxidative
stress, loss of cell function, and ultimately apoptosis or necrosis. A balance between oxidant
and antioxidant intracellular systems is hence vital for cell function, regulation, and
adaptation to diverse growth conditions. Thioredoxin reductase (TrxR) in conjunction with
thioredoxin (Trx) is a ubiquitous oxidoreductase system with antioxidant and redox regulatory
roles. In mammals, extracellular forms of Trx also have cytokine-like effects. Mammalian TrxR has
a highly reactive active site selenocysteine residue resulting in a profound reductive capacity,
reducing several substrates in addition to Trx. Due to the reactivity of TrxR, the enzyme is
inhibited by many clinically used electrophilic compounds including nitrosoureas,
aurothioglucose, platinum compounds, and retinoic acid derivatives. The properties of TrxR in
combination with the functions of Trx position this system at the core of cellular thiol redox
control and antioxidant defense. In this review, we focus on the reactions of the Trx system with
ROS molecules and different cellular antioxidant enzymes. We summarize the TrxR-catalyzed
regeneration of several antioxidant compounds, including ascorbic acid (vitamin C), selenium-
containing substances, lipoic acid, and ubiquinone (Q10). We also discuss the general cellular
effects of TrxR inhibition. Dinitrohalobenzenes constitute a unique class of immunostimulatory
TrxR inhibitors and we consider the immunomodulatory effects of dinitrohalobenzene compounds in
view of their reactions with the Trx system. (C) 2001 Elsevier Science Inc. 
thioredoxin; thioredoxin reductase; redox regulation; inflammation; oxidative stress; antioxidant; dinitrohalobenzene; reactive oxygen species; free radicals 
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