The Peroxiredoxin Repair Proteins

Jönsson, Thomas J.; Lowther, W. Todd

doi:10.1007/978-1-4020-6051-9_6

Cited by 65 publications

(53 citation statements)

References 77 publications

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“…The hyperoxidation of Prx could lead to the inactivation of Prx and their regeneration would require repair proteins such as sulfiredoxins and/or sestrins. In this regard, several studies have shown the regeneration process by monitoring the total and hyperoxidized forms of Prxs and used these varied forms of Prx to assess cellular Prx activity (27,38). Because the total amount of Prx remains unchanged over the same time course, our data suggest that the hyperoxidized forms are not targeted for degradation and most probably regenerated to their active forms.…”

Section: Indran Et Almentioning

confidence: 77%

hTERT Overexpression Alleviates Intracellular ROS Production, Improves Mitochondrial Function, and Inhibits ROS-Mediated Apoptosis in Cancer Cells

2011

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The human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the telomerase holoenzyme. Evidence is accumulating to link hTERT to activities other than telomere maintenance and immortalization. Here, we show that hTERT overexpression not only reduces the basal cellular reactive oxygen species (ROS) levels but also inhibits endogenous ROS production in response to stimuli that induce intracellular ROS generation. Conversely, siRNA-mediated gene silencing of hTERT potentiated the increase in cellular ROS levels following exposure to oxidative stress. This antioxidant effect of hTERT is mediated via a significant increase in the ratio of reduced to oxidized glutathione (GSH:GSSG) as well as efficient recovery of the oxidized peroxiredoxin to its nonoxidized form. Our data also provide evidence for mitochondrial localization of hTERT, and a significantly higher activity of cytochrome C oxidase, the rate-limiting enzyme in the mitochondrial electron transport chain, in hTERT overexpressing cells. To ascertain whether the improved mitochondrial function and antioxidant effect of hTERT could provide cancer cells with a survival advantage, the effect of oxidative stress on mitochondrial apoptosis was evaluated. Indeed, hTERT overexpressing cells inhibited cytosolic acidification, translocation of Bax, the drop in mitochondrial transmembrane potential, the release of cytochrome C to the cytosol, and cell death. Taken together, these data demonstrate a hitherto undefined role of hTERT in alleviating cellular ROS levels by way of potentiating the cellular antioxidant defense systems, and in doing so endowing cancer cells with the ability to evade death stimuli. Cancer Res; 71(1); 266-76. Ó2010 AACR.

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Section: Indran Et Almentioning

confidence: 77%

hTERT Overexpression Alleviates Intracellular ROS Production, Improves Mitochondrial Function, and Inhibits ROS-Mediated Apoptosis in Cancer Cells

2011

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“…Together with sulfiredoxins (Srx), SESNs function to repair overoxidized peroxiredoxins (Prx, a family of antioxidant enzymes that controls cytokine-induced peroxide levels) (35). There are three isoforms of SESN proteins: SESN1, SESN2, and SESN3, which are expressed ubiquitously in all adult tissues, although to different extents (36).…”

Section: Resultsmentioning

confidence: 99%

Gossypol Acetic Acid Prevents Oxidative Stress-Induced Retinal Pigment Epithelial Necrosis by Regulating the FoxO3/Sestrin2 Pathway

Hanus

Zhang

Chen

et al. 2015

Molecular and Cellular Biology

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The late stage of dry age-related macular degeneration (AMD), or geographic atrophy (GA), is characterized by extensive retinal pigment epithelial (RPE) cell death, and a cure is not available currently. We have recently demonstrated that RPE cells die from necrosis in response to oxidative stress, providing a potential novel mechanism for RPE death in AMD. In this study, we screened U.S. Food and Drug Administration-approved natural compounds and identified gossypol acetic acid (GAA) as a potent inhibitor of oxidative stress-induced RPE cell death. GAA induces antioxidative response and inhibits accumulation of excessive reactive oxygen species in cells, through which it prevents the activation of intrinsic necrotic pathway in response to oxidative stress. Sestrin2 (SESN2) is found to mediate GAA function in antioxidative response and RPE survival upon oxidative stress. Moreover, Forkhead box O3 transcription factor (FoxO3) is further found to be required for GAA-mediated SESN2 expression and RPE survival. Mechanistically, GAA promotes FoxO3 nuclear translocation and binding to the SESN2 enhancer, which in turn increases its transcriptional activity. Taken together, we have identified GAA as a potent inhibitor of oxidative stress-induced RPE necrosis by regulating the FoxO3/SESN2 pathway. This study may have significant implications in the therapeutics of age-related diseases, especially GA.A ge-related macular degeneration (AMD) is the leading cause of severe vision loss in people aged over 50, and its prevalence increases exponentially in people over the age of 70 (1). Currently, it is estimated that 1.75 million individuals suffer from this disease in the United States, and 7 million are said to be "at risk" (2). There are two types of AMD, the "dry" and "wet" forms, respectively. Dry AMD is a chronic disease that usually causes some degree of visual impairment and sometimes progresses to severe blindness. Dry AMD accounts for 90% of AMD cases and is currently without treatment available. The late stage of dry AMD, which is also knows as geographic atrophy (GA), is characterized by scattered or confluent areas of degeneration of retinal pigment epithelium (RPE) cells and the overlying photoreceptors that rely on the RPE for trophic support (3). AMD is a multifactorial disease with unclear etiology. Age is the most consistent risk factor associated with AMD, and genetic factors, oxidative stress, and inflammation also significantly contribute to AMD pathogenesis (4). Cigarette smoking, which induces systemic oxidative stress, has been proved to be a significant risk factor for AMD. Consistently, clinical studies have shown that the progression of AMD can be slowed with antioxidant vitamins and zinc supplements (5, 6). The retina is one of the highest oxygen-consuming tissues in the human body and, in particular, RPE is vulnerable to oxidative damage (7,8). The mechanism of RPE cell death in response to oxidative stress and in GA has been controversial. Apoptosis was suggested as a major mechanism of RPE cell ...

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“…Thioredoxin and peroxiredoxins, by using redox-active cysteines rather than selenium, reduce hydrogen peroxide and organic peroxides. The active form of thioredoxin is recovered by selenoprotein thioredoxin reductase (Forman et al 2002(Forman et al , 2004, while oxidized peroxiredoxins are reduced by thiols such as GSH, or ascorbic acid (Monteiro et al 2007, Jönsson andLowther 2007). Thioredoxin and peroxiredoxins have not been investigated in celiac disease yet.…”

Section: Discussionmentioning

confidence: 99%

Glutathione redox cycle in small intestinal mucosa and peripheral blood of pediatric celiac disease patients

Stojiljković

Pejić

Kasapović

et al. 2012

An. Acad. Bras. Ciênc.

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The celiac disease is an autoimmune gastrointestinal disorder caused by gluten from wheat, rye or barley. In genetically predisposed persons, gluten induces the immune-mediated inflammation of small intestinal mucosa. Histological lesions include intraepithelial lymphocytosis, crypt hypertrophy and villous atrophy, resulting in malabsorption of micro-and macronutrients. The only treatment for celiac patients is a permanent gluten-free diet (GFD). Reactive oxygen species (ROS) and oxidative stress are strongly associated with the celiac disease. Glutathione (GSH) is a main detoxifier of endogenous and exogenous ROS in the intestine. In order to explain the role of glutathione redox cycle in celiac patients, we examined the activities of GSHrelated antioxidant (AO) enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the concentration of GSH in small intestinal biopsies and peripheral blood of children affected by the celiac disease. The concentration of lipid hydroperoxides (LOOH) as markers of oxidative damage was measured in the same samples. The results clearly demonstrate a significant malfunction of GSH redox cycle with a concomitant decrease in the capacity to regenerate GSH and detoxify LOOH in celiac patients, even after several years of GFD. The oral administration of GSH and a diet rich in natural antioxidants, as well as appropriate dietary supplements, could be of great benefit to the patients.

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The Peroxiredoxin Repair Proteins

Cited by 65 publications

References 77 publications

hTERT Overexpression Alleviates Intracellular ROS Production, Improves Mitochondrial Function, and Inhibits ROS-Mediated Apoptosis in Cancer Cells

hTERT Overexpression Alleviates Intracellular ROS Production, Improves Mitochondrial Function, and Inhibits ROS-Mediated Apoptosis in Cancer Cells

Gossypol Acetic Acid Prevents Oxidative Stress-Induced Retinal Pigment Epithelial Necrosis by Regulating the FoxO3/Sestrin2 Pathway

Glutathione redox cycle in small intestinal mucosa and peripheral blood of pediatric celiac disease patients

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