Peroxiredoxin 6, a 1-Cys peroxiredoxin, functions in antioxidant defense and lung phospholipid metabolism☆

Manevich, Yefim; Fisher, Aron B.

doi:10.1016/j.freeradbiomed.2005.02.011

Cited by 349 publications

(355 citation statements)

References 70 publications

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“…Oxidation of the catalytic cysteine of 1-cysPrx has been associated with its loss of peroxidase activity (Manevich and Fisher, 2005 activity (Manevich and Fisher, 2005). From this study, it was concluded that the glutathionylation and subsequent GSH-mediated reduction of 1-cysPrx requires heterodimerization with GSTp (Manevich and Fisher, 2005).…”

Section: Gsts and Kinase Regulationmentioning

confidence: 88%

Glutathione S-transferase polymorphisms: cancer incidence and therapy

2006

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The super family of glutathione S-transferases (GSTs) is composed of multiple isozymes with significant evidence of functional polymorphic variation. Over the last three decades, data from cancer studies have linked aberrant expression of GST isozymes with the development and expression of resistance to a variety of chemicals, including cancer drugs. This review addresses how differences in the human GST isozyme expression patterns influence cancer susceptibility, prognosis and treatment. In addition to the well-characterized catalytic activity, recent evidence has shown that certain GST isozymes can regulate mitogen-activated protein kinases or can facilitate the addition of glutathione to cysteine residues in target proteins (S-glutathionylation). These multiple functionalities have contributed to the recent efforts to target GSTs with novel small molecule therapeutics. Presently, at least two drugs are in latestage clinical testing. The evolving functions of GST and their divergent expression patterns in individuals make them an attractive target for drug discovery.

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Section: Gsts and Kinase Regulationmentioning

confidence: 88%

Glutathione S-transferase polymorphisms: cancer incidence and therapy

2006

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“…GS-ylation of p65-NF-B potentiates hypoxic apoptosis in murine embryonic fibroblasts (143). Furthermore, the discovery that GST can bind to Sglutathionyl groups on proteins (30) and that GST can transfer GSH to restore Prx6 activity (117) suggests that GST could catalyze GS-ylation. If so, different GST proteins could regulate cell functions by GS-ylation of different subsets of proteins.…”

Section: Gsh and Trxs As Common Control Nodes For Protein Thiol Redoxmentioning

confidence: 99%

Radical-free biology of oxidative stress

Jones¹

2008

American Journal of Physiology-Cell Physiology

1,020

839

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Free radical-induced macromolecular damage has been studied extensively as a mechanism of oxidative stress, but large-scale intervention trials with free radical scavenging antioxidant supplements show little benefit in humans. The present review summarizes data supporting a complementary hypothesis for oxidative stress in disease that can occur without free radicals. This hypothesis, which is termed the "redox hypothesis," is that oxidative stress occurs as a consequence of disruption of thiol redox circuits, which normally function in cell signaling and physiological regulation. The redox states of thiol systems are sensitive to twoelectron oxidants and controlled by the thioredoxins (Trx), glutathione (GSH), and cysteine (Cys). Trx and GSH systems are maintained under stable, but nonequilibrium conditions, due to a continuous oxidation of cell thiols at a rate of about 0.5% of the total thiol pool per minute. Redox-sensitive thiols are critical for signal transduction (e.g., H-Ras, PTP-1B), transcription factor binding to DNA (e.g., Nrf-2, nuclear factor-B), receptor activation (e.g., ␣IIb␤3 integrin in platelet activation), and other processes. Nonradical oxidants, including peroxides, aldehydes, quinones, and epoxides, are generated enzymatically from both endogenous and exogenous precursors and do not require free radicals as intermediates to oxidize or modify these thiols. Because of the nonequilibrium conditions in the thiol pathways, aberrant generation of nonradical oxidants at rates comparable to normal oxidation may be sufficient to disrupt function. Considerable opportunity exists to elucidate specific thiol control pathways and develop interventional strategies to restore normal redox control and protect against oxidative stress in aging and age-related disease.thioredoxin; glutathione; cysteine; hydrogen peroxide; redox signaling; protein thiol ONE OF THE GREAT REDOX BIOLOGISTS of the past century, Howard S. Mason, professed that to advance science, a scientist must interpret observations at the limit of their meaning. The present review of the redox biology of thiol systems addresses the possibility that disruption of the function and homeostasis of thiol systems is the most central feature of oxidative stress that contributes to mechanisms of aging and age-related disease. I have termed this the "redox hypothesis" to facilitate distinction from free radical hypotheses.Many proteins contain redox-sensitive thiols, and reactions of thiol systems occur largely by nonradical two-electron transfers. Accumulating data show that central thiol-disulfide couples are maintained under nonequilibrium conditions in biological systems. This presents a condition wherein changes in abundance and distribution of redox catalysts and changes in rates of generation of relevant oxidants (e.g., peroxides) and precursors for NADPH supply can account for pathological effects of oxidative stress through altered functions of enzymes, receptors, transporters, transcription factors, and structural elements, without free ra...

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“…Among these candidate TAAs were PRDX6/AOP2, clusterin, DJ-1, superoxide dismutase, alcohol dehydrogenase, heat shock proteins, and lactoylglutathione lyase. As mentioned above, PRDX6/AOP2 is transcriptionally regulated by LEDGF/p75 and plays an important role in antioxidant defense (86,99). Interestingly, loss of the homeobox gene Nkx3.1 in mice is associated with loss of PRDX6/AOP2 and promotes increased oxidative damage in prostate carcinogenesis (100).…”

Section: Cancer-associated Autoantibodies As Reporters Of Tumorigenesismentioning

confidence: 99%

Tumor-associated Antigen Arrays for the Serological Diagnosis of Cancer

Casiano

Mediavilla-Varela

Tan

2006

Molecular & Cellular Proteomics

122

106

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The recognition that human tumors stimulate the production of autoantibodies against autologous cellular proteins called tumor-associated antigens (TAAs) has opened the door to the possibility that autoantibodies could be exploited as serological tools for the early diagnosis and management of cancer. Cancer-associated autoantibodies are often driven by intracellular proteins that are mutated, modified, or aberrantly expressed in tumor cells and hence are regarded as immunological reporters that could help uncover molecular events underlying tumorigenesis. Emerging evidence suggests that each type of cancer might trigger unique autoantibody signatures that reflect the nature of the malignant process in the affected organ. The advent of novel genomic, proteomic, and high throughput approaches has accelerated interest in the serum autoantibody repertoire in human cancers for the discovery of candidate TAAs. The use of individual anti-TAA autoantibodies as diagnostic or prognostic tools has been tempered by their low frequency and heterogeneity in most human cancers. However, TAA arrays comprising several antigens significantly increase this frequency and hold great promise for the early detection of cancer, monitoring cancer progression, guiding individualized therapeutic interventions, and identification of novel therapeutic targets. Our recent studies suggest that the implementation of TAA arrays in screening programs for the diagnosis of prostate cancer and other cancers should be preceded by the optimization of their sensitivity and specificity through the careful selection of the most favorable combinations of TAAs.

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Peroxiredoxin 6, a 1-Cys peroxiredoxin, functions in antioxidant defense and lung phospholipid metabolism☆

Cited by 349 publications

References 70 publications

Glutathione S-transferase polymorphisms: cancer incidence and therapy

Glutathione S-transferase polymorphisms: cancer incidence and therapy

Radical-free biology of oxidative stress

Tumor-associated Antigen Arrays for the Serological Diagnosis of Cancer

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