Anti-oxidative, anti-cancer and anti-inflammatory actions by thioredoxin 1 and thioredoxin-binding protein-2.

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.

• Authors: Rie Watanabe, Hajime Nakamura, Hiroshi Masutani, Junji Yodoi
• Journal: Pharmacology & therapeutics (Pharmacol Ther) Vol. 127 Issue 3 Pg. 261-70 (Sep 2010) ISSN: 1879-016X [Electronic] England
• PMID: 20435060 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: 2010 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antineoplastic Agents
• Carrier Proteins
• Recombinant Proteins
• TXNIP protein, human
• Thioredoxins

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects, physiology)
• Carrier Proteins (genetics, metabolism, physiology)
• Cell Proliferation (drug effects)
• Humans
• Metabolic Diseases (drug therapy, metabolism, pathology)
• Neoplasms (drug therapy, metabolism, pathology)
• Oxidative Stress (physiology)
• Recombinant Proteins (genetics, pharmacology, therapeutic use)
• Thioredoxins (genetics, metabolism, pharmacology, physiology, therapeutic use)
• Up-Regulation