Abstract
Thioredoxin 1 (Trx 1) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys- that is ubiquitously present in the human body. Trx 1 is a defensive protein induced by various stresses and has anti-oxidative, anti-apoptotic and anti-inflammatory effects. The anti-oxidative effect of Trx 1 is mediated by the dithiol-disulfide exchange in the active site. Trx 1 is able to interact with certain molecules, one of which is thioredoxin-binding protein-2 (TBP-2)/Vitamin D3 upregulated protein 1 (VDUP1)/thioredoxin interacting protein (TXNIP). TBP-2 was originally identified as a negative regulator of Trx 1 and acts as a cell growth suppressor and a regulator in lipid/glucose metabolism. Trx 1 and TBP-2 play crucial roles in pathophysiological mechanisms in metabolic disorders, cancer and inflammation. Here we discuss pharmacological aspects of Trx 1 and TBP-2 in these diseases and propose potential therapeutic approaches for intractable oxidative stress-related disorders.
2010 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Apoptosis / drug effects
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Apoptosis / physiology
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Carrier Proteins / physiology*
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Cell Proliferation / drug effects
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Humans
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Metabolic Diseases / drug therapy
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Metabolic Diseases / metabolism*
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Metabolic Diseases / pathology
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Neoplasms / drug therapy
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Neoplasms / metabolism*
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Neoplasms / pathology
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Oxidative Stress / physiology*
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Recombinant Proteins / genetics
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Recombinant Proteins / pharmacology
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Recombinant Proteins / therapeutic use
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Thioredoxins / genetics
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Thioredoxins / metabolism
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Thioredoxins / pharmacology
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Thioredoxins / physiology*
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Thioredoxins / therapeutic use
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Up-Regulation
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Antineoplastic Agents
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Carrier Proteins
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Recombinant Proteins
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TXNIP protein, human
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Thioredoxins