ESSENTIALS OF ANTIOXIDANT BIOLOGY AND MEDICINE by Unknown

Author:Unknown
Language: eng
Format: epub
Published: 0101-01-01T00:00:00+00:00

UNIT IV

The thioredoxin system

Chapter 11. Thioredoxin

HIGHLIGHTS

§ Thioredoxin (Trx) refers to a class of small redox proteins that undergo NADPH-dependent reduction by thioredoxin reductase (TrxR) and in turn reduce the disulfide bridge in target proteins. Mammalian Trxs include two isozymes, namely, Trx1 and Trx2.

§ In addition to directly scavenging reactive oxygen species (ROS), Trxs serve as cofactors for various enzymes, including ribonucleotide reductase, peroxiredoxins, and glutathione peroxidase 3. Trxs also modulate the activity of many transcription factors.

§ Studies in animal models have shown that both Trx1 and Trx2 protect against disease conditions that involve oxidative and inflammatory stress, especially cardiovascular disorders. On the other hand, Trxs may promote cancer development under certain conditions.

§ The exact role of Trxs in human health and disease remains largely unknown.

keywords | DNA synthesis; Molecular regulation; Nuclear factor E2-related factor 2; Oxidative stress; Protein denitrosylation; Redox protein; Redox signaling; Ribonucleotide reductase; Thioredoxin; Tumorigenesis

CITATION | Hopkins RZ and Li YR. Essentials of Antioxidant Biology and Medicine. Cell Med Press, Raleigh, NC, USA. 2020. http://dx.doi.org/10.20455/eabm.2020

ABBREVIATIONS | ARE, antioxidant response element; ASK1, apoptosis signal-regulating kinase 1; GPx3, glutathione peroxidase 3; mTOR, mechanistic target of rapamycin; Nrf2, nuclear factor E2-related factor 2; ROS, reactive oxygen species; Trx, thioredoxin; TrxR, thioredoxin reductase; Txnip, thioredoxin-interacting protein

CONTENTS

1. Overview

2. History

3. Biochemistry

4. Molecular Regulation

4.1. Nrf2 Signaling

4.2. Other Regulatory Mechanisms

5. Biology and Medicine

5.1. Antioxidant Functions

5.1.1. Mechanisms of Antioxidative Effects

5.1.2. Role of Trx1 in Protecting against Oxidative Disease Processes

5.1.3. Role of Trx2 in Protecting against Oxidative Disease Processes

5.2. Role in Embryonic Development

5.3. Role in Cell Signaling

5.4. Role in Cancer Development

6. Conclusion and Perspective

7. Self-Assessment Questions

1. OVERVIEW

The term thioredoxin (Trx) refers to a class of small redox proteins (~12 kDa) that undergo NADPH-dependent reduction by thioredoxin reductase (TrxR; see Chapter 13 on TrxR) and in turn reduce the disulfide bridge in target proteins. Currently, there are two Trxs in mammals: Trx1 and Trx2. They are ubiquitously distributed in mammalian tissues. Trx1 is predominantly located in the cytosol and can be also excreted into the extracellular space or translocate into the nucleus, whereas Trx2 is present in the mitochondrion. In humans, Trx1 and Trx2 are localized on chromosomes 9q13 and 22q13.1, respectively. Table 11.1 summarizes the basic characteristics of mammalian Trxs. It should be noted that the term ‘thioredoxin superfamily’ is often encountered in the literature and refers to a large group of proteins, including Trxs, glutaredoxins (see Chapter 10 ), and protein disulfide isomerases (PDIs).

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