Thioredoxin System in Cell Death Progression DOI
Jun Lu, Arne Holmgren

Antioxidants and Redox Signaling, Journal Year: 2012, Volume and Issue: 17(12), P. 1738 - 1747

Published: April 24, 2012

The thioredoxin (Trx) system, comprising nicotinamide adenine dinucleotide phosphate, Trx reductase (TrxR), and Trx, is critical for maintaining cellular redox balance antioxidant function, including control of oxidative stress cell death.Here, we focus on the research progress that involved in regulation apoptosis by systems. In mammalian cells, cytosolic Trx1 mitochondrial Trx2 systems are major disulfide reductases supplying electrons to enzymes proliferation viability. reduced/dithiol form Trxs binds signal-regulating kinase 1 (ASK1) inhibits its activity prevent stress- cytokine-induced apoptosis. When oxidized, it dissociates from ASK1 stimulated. binding inhibitor interacting protein (TXNIP) also contributes process removing ASK1. TrxRs large homodimeric selenoproteins with an overall structure which similar glutathione reductase, contain active site GCUG C-terminus.In death processes, state TrxR activities key factors determine fate. high reactivity Sec accessible location make emerge as targets pharmaceutic drugs. inactivation covalent modification does not only change but may convert into a reactive oxygen species generator. Numerous electrophilic compounds some environmental toxins pharmaceutical drugs inhibit TrxR. We have classified these four types propose useful principles understand reaction mechanism inhibition compounds.

Language: Английский

Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal DOI Creative Commons
Antonio Ayala, Mario Muñoz, Sandro Argüelles

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2014, Volume and Issue: 2014, P. 1 - 31

Published: Jan. 1, 2014

Lipid peroxidation can be described generally as a process under which oxidants such free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid has shown its important role in cell biology and human health. Since early 1970s, total published research articles on topic was 98 (1970–1974) been increasing at almost 135-fold, by up to 13165 4 years (2010–2013). New discoveries about involvement cellular physiology pathology, well control peroxidation, continue emerge every day. Given enormity this field, review focuses biochemical concepts production, metabolism, signaling mechanisms two main omega-6 products: malondialdehyde (MDA) and, particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only physiological protective function molecule stimulating gene expression survival, but also cytotoxic inhibiting promoting death. Finally, overviews vivo mammalian model systems used study process, common pathological processes linked MDA 4-HNE are shown.

Language: Английский

Citations

5093
The thioredoxin antioxidant system DOI
Jun Lu, Arne Holmgren

Free Radical Biology and Medicine, Journal Year: 2013, Volume and Issue: 66, P. 75 - 87

Published: July 27, 2013

Language: Английский

Citations

1745
Free radicals, reactive oxygen species, oxidative stress and its classification DOI
Volodymyr I. Lushchak

Chemico-Biological Interactions, Journal Year: 2014, Volume and Issue: 224, P. 164 - 175

Published: Oct. 28, 2014

Language: Английский

Citations

1409
Beyond oxidative stress: an immunologist's guide to reactive oxygen species DOI
Carl Nathan, Amy Cunningham‐Bussel

Nature reviews. Immunology, Journal Year: 2013, Volume and Issue: 13(5), P. 349 - 361

Published: April 25, 2013

Language: Английский

Citations

1386
Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions DOI Creative Commons
Volodymyr I. Lushchak

Journal of Amino Acids, Journal Year: 2012, Volume and Issue: 2012, P. 1 - 26

Published: Feb. 28, 2012

Glutathione (GSH) is a tripeptide, which has many biological roles including protection against reactive oxygen and nitrogen species. The primary goal of this paper to characterize the principal mechanisms protective role GSH species electrophiles. ancillary goals are provide up-to-date knowledge biosynthesis, hydrolysis, utilization; intracellular compartmentalization interorgan transfer; elimination endogenously produced toxicants; involvement in metal homeostasis; glutathione-related enzymes their regulation; glutathionylation sulfhydryls. Individual sections devoted relationships between homeostasis pathologies as well developed research tools pharmacological approaches manipulating levels. Special attention paid compounds mainly natural origin (phytochemicals) affect GSH-related processes. provides starting points for development novel hypothesis investigation physiology biochemistry glutathione with focus on human animal health.

Language: Английский

Citations

1123
The cytoprotective role of the Keap1–Nrf2 pathway DOI

Liam Baird,

Albena T. Dinkova‐Kostova

Archives of Toxicology, Journal Year: 2011, Volume and Issue: 85(4), P. 241 - 272

Published: March 2, 2011

Language: Английский

Citations

928
Glutathione and Thioredoxin Antioxidant Pathways Synergize to Drive Cancer Initiation and Progression DOI Creative Commons
Isaac S. Harris,

Aislinn E. Treloar,

Satoshi Inoue

et al.

Cancer Cell, Journal Year: 2015, Volume and Issue: 27(2), P. 211 - 222

Published: Jan. 22, 2015

Language: Английский

Citations

834
The role of glutathione reductase and related enzymes on cellular redox homoeostasis network DOI
Narciso Couto, Jennifer A. Wood, Jill Barber

et al.

Free Radical Biology and Medicine, Journal Year: 2016, Volume and Issue: 95, P. 27 - 42

Published: Feb. 27, 2016

Language: Английский

Citations

821
Selenium and selenocysteine: roles in cancer, health, and development DOI

Dolph L. Hatfield,

Petra A. Tsuji,

Bradley A. Carlson

et al.

Trends in Biochemical Sciences, Journal Year: 2014, Volume and Issue: 39(3), P. 112 - 120

Published: Jan. 29, 2014

Language: Английский

Citations

641
Role of Glutathione in Cancer: From Mechanisms to Therapies DOI Creative Commons
Luke Kennedy, Jagdeep K. Sandhu, Mary‐Ellen Harper

et al.

Biomolecules, Journal Year: 2020, Volume and Issue: 10(10), P. 1429 - 1429

Published: Oct. 9, 2020

Glutathione (GSH) is the most abundant non-protein thiol present at millimolar concentrations in mammalian tissues. As an important intracellular antioxidant, it acts as a regulator of cellular redox state protecting cells from damage caused by lipid peroxides, reactive oxygen and nitrogen species, xenobiotics. Recent studies have highlighted importance GSH key signal transduction reactions controller cell differentiation, proliferation, apoptosis, ferroptosis immune function. Molecular changes antioxidant system disturbances homeostasis been implicated tumor initiation, progression, treatment response. Hence, has both protective pathogenic roles. Although healthy crucial for removal detoxification carcinogens, elevated levels are associated with progression increased resistance to chemotherapeutic drugs. Recently, several novel therapies developed target tumors means response decreased drug resistance. In this comprehensive review we explore mechanisms functionalities different therapeutic approaches that either directly, indirectly or use GSH-based prodrugs. Consideration also given computational methods used describe related processes silico testing effects.

Language: Английский

Citations

589