Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression

Neumann, Carola A.; Krause, Daniela; Carman, Christopher V.; Das, Shampa; Dubey, Devendra P.; Abraham, Jennifer L.; Bronson, Roderick T.; Fujiwara, Yuko; Orkin, Stuart H.; Etten, Richard A. Van

doi:10.1038/nature01819

Cited by 717 publications

(578 citation statements)

References 29 publications

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“…Thereby, we identified a set of candidate genes showing significantly reduced mRNA expression levels in 1p/19q-deleted as compared with 1p/19q-intact tumours (Tews et al, 2006). These included the CITED4 gene at 1p34.2 (Tews et al, 2007) as well as several other genes, among which the peroxiredoxin 1 (PRDX1) gene appeared as a particular promising candidate because (i) it was independently identified in a proteomic screen of lowgrade oligodendroglial tumours (Grzendowski et al, 2010), (ii) was reported to have tumour-preventive functions (Neumann et al, 2003) and (iii) was linked to radiotherapy response of cancer cells Zhang et al, 2008). Here, we report on the mechanism leading to the frequent downregulation of PRDX1 mRNA and proteins in 1p/19q-deleted gliomas and provide first evidence for a role of peroxiredoxin 1 in the response of Hs683 glioma cells to TMZ and ionizing irradiation.…”

Section: Discussionmentioning

confidence: 99%

“…The finding that loss of Prdx1 in mice leads to premature death from cancer clearly indicates a tumour-preventive function (Neumann et al, 2003). However, PRDX1 may also support survival of cancer cells and tumour growth by scavenging H 2 O 2 and thereby protecting tumour cells from ROS-induced cell death.…”

Section: Discussionmentioning

confidence: 99%

“…It functions as a thiol reductase involved in oxidative stress defense mechanisms through its ability to catalyse peroxide reduction of reactive oxygen species (ROS), such as H 2 O 2 , organic hydroperoxides and peroxynitrite (for review see Immenschuh and Baumgart-Vogt, 2005). Prdx1 knockout mice have higher levels of cellular ROS and die prematurely of cancer, indicating a tumour-preventive role of peroxiredoxin 1 (Neumann et al, 2003). More recently, peroxiredoxin 1 has been reported to inhibit tumourigenesis by binding the tumour suppressor PTEN and protecting PTEN from oxidation-induced inactivation (Cao et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro

et al. 2011

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Deletions of chromosomal arms 1p and 19q are frequent in oligodendroglial tumours and linked to radio-and chemotherapy response as well as longer survival. The molecular mechanisms underlying this clinically important association are as yet unknown. Here, we studied the peroxiredoxin 1 (PRDX1) gene at 1p34.1 for promoter methylation and expression in primary gliomas and investigated its role in radio-and chemosensitivity of glioma cells in vitro. In total, we screened primary glioma tissues from 93 patients for methylation of the 5 0 -CpG island of PRDX1 by sodium bisulfite sequencing. PRDX1 mRNA and protein expression levels were determined in subsets of the tumours by quantitative PCR and western blot analysis, respectively. PRDX1 hypermethylation and reduced expression were frequently detected in oligodendroglial tumours and secondary glioblastomas, but not in primary glioblastomas. In oligodendroglial tumours, both PRDX1 hypermethylation and reduced mRNA expression were significantly associated with 1p/19q-deletion. Stable knockdown of PRDX1 by lentiviral transduction of shorthairpin (sh)RNA constructs significantly increased apoptosis and reduced cell viability of Hs683 glioma cells exposed to ionizing irradiation or temozolomide in vitro. Taken together, our findings indicate that epigenetic silencing of PRDX1 is frequent in 1p/19q-deleted oligodendroglial tumours and likely contributes to radioand chemosensitivity of these tumours.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro

et al. 2011

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“…Reduced lifespan observed in SOD1 −/− ,27 PRX1 −/− ,250 PRX2 −/− 251 and TRX2 +/− 252 models is much more prominent in the SOD1 −/− rodent model,281 indicating that specific key RONS regulatory systems and redox signalling pathways are implicated in the processes of ageing. Moreover, although indistinguishable from WT mice at birth, by 5–8 months of age, SOD1 −/− mice show an accelerated neuromuscular ageing phenotype associated with myofibre atrophy (Figure 5), neurological impairments (Figure 6) and functional deficits 275.…”

Section: Non‐enzymatic Key Antioxidants That Contribute To the Maintementioning

confidence: 97%

“…SOD1 −/− ,27 PRX1 −/− ,250 PRX2 −/− ,251 TRX2 +/− 252 and MSRA −/− 253 rodent models show a reduction in lifespan; in contrast, more recent studies have reported no effect of MSRA −/− on rodent lifespan 254. GPX1 −/− ,28, 252 SOD2 +/− ,240 extracellular SOD −/− 255, 256 and MSRB −/− 257 knockout murine models show no effect on lifespan.…”

Section: Non‐enzymatic Key Antioxidants That Contribute To the Maintementioning

confidence: 99%

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Sakellariou

Lightfoot

Earl

et al. 2017

J cachexia sarcopenia muscle

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Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age‐related muscle atrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributor to morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population (estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associated with neuromuscular ageing, will inevitably increase. Despite the importance of this ‘epidemic’ problem, the primary biochemical and molecular mechanisms underlying age‐related deficits in neuromuscular integrity and function have not been fully determined. Skeletal muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age‐associated oxidative damage has been suggested to be a major factor contributing to the initiation and progression of muscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, and disruption of these events over time due to altered redox control has been proposed as an underlying mechanism of ageing. The role of oxidants in ageing has been extensively examined in different model organisms that have undergone genetic manipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function of RONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redox homeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken in murine models to examine the role of redox regulation in age‐related muscle atrophy and weakness.

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Overview of Peroxiredoxins in Oxidant Defense and Redox Regulation

2011

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Peroxiredoxins are important hydroperoxide detoxification enzymes, yet have only come to the fore in recent years relative to the other major players in peroxide detoxification, heme-containing catalases and peroxidases, and glutathione peroxidases. These cysteine-dependent peroxidases exhibit high reactivity with hydrogen peroxide, organic hydroperoxides and peroxynitrite and play major roles not only in peroxide defense, but also in regulating peroxide-mediated cell signaling. This overview focuses on important peroxiredoxin features that have emerged over the past several decades with an emphasis on catalytic mechanism, regulation and biological function.

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Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression

Cited by 717 publications

References 29 publications

Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro

Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Overview of Peroxiredoxins in Oxidant Defense and Redox Regulation

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