scholarly journals Reactive Oxygen Species-mediated β-Cleavage of the Prion Protein in the Cellular Response to Oxidative Stress

2005 ◽  
Vol 280 (43) ◽  
pp. 35914-35921 ◽  
Author(s):  
Nicole T. Watt ◽  
David R. Taylor ◽  
Andrew Gillott ◽  
Daniel A. Thomas ◽  
W. Sumudhu S. Perera ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Prion Protein ◽  
Cellular Response ◽  
Prion Diseases ◽  
Physiological Role ◽  
Reactive Oxygen ◽  
Cellular Prion Protein ◽  
Critical Event ◽  
Oxygen Species

The cellular prion protein (PrPC) is critical for the development of prion diseases. However, the physiological role of PrPC is less clear, although a role in the cellular resistance to oxidative stress has been proposed. PrPC is cleaved at the end of the copper-binding octapeptide repeats through the action of reactive oxygen species (ROS), a process termed β-cleavage. Here we show that ROS-mediated β-cleavage of cell surface PrPC occurs within minutes and was inhibited by the hydroxyl radical quencher dimethyl sulfoxide and by an antibody against the octapeptide repeats. A construct of PrP lacking the octapeptide repeats, PrPΔoct, failed to undergo ROS-mediated β-cleavage, as did two mutant forms of PrP, PG14 and A116V, associated with human prion diseases. As compared with cells expressing wild type PrP, when challenged with H2O2 and Cu2+, cells expressing PrPΔoct, PG14, or A116V had reduced viability and glutathione peroxidase activity and increased intracellular free radicals. Thus, lack of ROS-mediated β-cleavage of PrP correlated with the sensitivity of the cells to oxidative stress. These data indicate that the β-cleavage of PrPC is an early and critical event in the mechanism by which PrP protects cells against oxidative stress.

Reactive oxygen species (ROS)-mediated β-cleavage of the prion protein in the mechanism of the cellular response to oxidative stress

2005 ◽  
Vol 33 (5) ◽  
pp. 1123-1125 ◽  
Author(s):  
N.T. Watt ◽  
N.M. Hooper
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Prion Protein ◽  
Cellular Response ◽  
Reactive Oxygen ◽  
Protective Role ◽  
Oxygen Species ◽  
Mutant Proteins ◽  
Functional Consequences ◽  
Conformational Conversion

The PrPC [cellular isoform of PrP (prion protein)] can undergo a conformational conversion to produce a proteinase-resistant form PrPSc (scrapie isoform of PrP), a step critical for the development of prion disease. Although essential for disease progression, the normal cellular function of PrPC remains unknown. Suggestions to date have centred on a protective role against oxidative stress. We have demonstrated that ROS (reactive oxygen species)-mediated β-cleavage of PrPC occurs at the cell surface, can be inhibited following hydroxyl radical quenching and has a prerequisite for the octarepeat region in the N-terminus of the protein. Significantly, two disease-associated mutants of PrP, namely PG14 and A116V (Ala116→Val), were unable to undergo β-cleavage and this lack of proteolysis was accompanied by functional consequences in cells expressing these mutant proteins. The cells were found to be less viable following exposure to copper and H2O2, had reduced levels of glutathione peroxidase and increased amounts of intracellular oxygen radicals. These results suggest that β-cleavage of PrPC is an initial consequence following exposure to ROS in the extracellular environment contributing to a pathway involved in antioxidant protection of neuronal cells.

scholarly journals Transcriptional Homeostasis of Oxidative Stress-Related Pathways in Altered Gravity

2018 ◽  
Vol 19 (9) ◽  
pp. 2814 ◽  
Author(s):  
Svantje Tauber ◽  
Swantje Christoffel ◽  
Cora Thiel ◽  
Oliver Ullrich
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Immune System ◽  
Cellular Response ◽  
Cultured Cells ◽  
Parabolic Flight ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Altered Gravity ◽  
Human Immune System

Whereby several types of cultured cells are sensitive to gravity, the immune system belongs to the most affected systems during spaceflight. Since reactive oxygen species/reactive nitrogen species (ROS/RNS) are serving as signals of cellular homeostasis, particularly in the cells of the immune system, we investigated the immediate effect of altered gravity on the transcription of 86 genes involved in reactive oxygen species metabolism, antioxidative systems, and cellular response to oxidative stress, using parabolic flight and suborbital ballistic rocket experiments and microarray analysis. In human myelomonocytic U937 cells, we detected a rapid response of 19.8% of all of the investigated oxidative stress-related transcripts to 1.8 g of hypergravity and 1.1% to microgravity as early as after 20 s. Nearly all (97.2%) of the initially altered transcripts adapted after 75 s of hypergravity (max. 13.5 g), and 100% adapted after 5 min of microgravity. After the almost complete adaptation of initially altered transcripts, a significant second pool of differentially expressed transcripts appeared. In contrast, we detected nearly no response of oxidative stress-related transcripts in human Jurkat T cells to altered gravity. In conclusion, we assume a very well-regulated homeostasis and transcriptional stability of oxidative stress-related pathways in altered gravity in cells of the human immune system.

scholarly journals Interaction of Oxidative Stress and Misfolded Proteins in the Mechanism of Neurodegeneration

Life ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 101 ◽  
Author(s):  
Andrey Y. Abramov ◽  
Elena V. Potapova ◽  
Viktor V. Dremin ◽  
Andrey V. Dunaev
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Free Radicals ◽  
Neurodegenerative Disorders ◽  
Structural Changes ◽  
Wide Spectrum ◽  
Physiological Role ◽  
Reactive Oxygen ◽  
Misfolded Proteins ◽  
Oxygen Species

Aggregation of the misfolded proteins β-amyloid, tau, huntingtin, and α-synuclein is one of the most important steps in the pathology underlying a wide spectrum of neurodegenerative disorders, including the two most common ones—Alzheimer’s and Parkinson’s disease. Activity and toxicity of these proteins depends on the stage and form of aggregates. Excessive production of free radicals, including reactive oxygen species which lead to oxidative stress, is proven to be involved in the mechanism of pathology in most of neurodegenerative disorders. Both reactive oxygen species and misfolded proteins play a physiological role in the brain, and only deregulation in redox state and aggregation of the proteins leads to pathology. Here, we review the role of misfolded proteins in the activation of ROS production from various sources in neurons and glia. We discuss if free radicals can influence structural changes of the key toxic intermediates and describe the putative mechanisms by which oxidative stress and oligomers may cause neuronal death.

Cellular prion protein protects against reactive-oxygen-species-induced DNA damage

2007 ◽  
Vol 43 (6) ◽  
pp. 959-967 ◽  
Author(s):  
Nicole T. Watt ◽  
Michael N. Routledge ◽  
Christopher P. Wild ◽  
Nigel M. Hooper
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Prion Protein ◽  
Reactive Oxygen ◽  
Cellular Prion Protein ◽  
Oxygen Species

Oxidative stress and reactive oxygen species: a review of their role in ocular disease

2017 ◽  
Vol 131 (24) ◽  
pp. 2865-2883 ◽  
Author(s):  
Lawson Ung ◽  
Ushasree Pattamatta ◽  
Nicole Carnt ◽  
Jennifer L. Wilkinson-Berka ◽  
Gerald Liew ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Function ◽  
Physiological Role ◽  
Reactive Oxygen ◽  
Age Related Macular Degeneration ◽  
Current Evidence ◽  
Oxygen Species ◽  
Age Related

For many years, oxidative stress arising from the ubiquitous production of reactive oxygen species (ROS) has been implicated in the pathogenesis of various eye diseases. While emerging research has provided some evidence of the important physiological role of ROS in normal cell function, disease may arise where the concentration of ROS exceeds and overwhelms the body’s natural defence against them. Additionally, ROS may induce genomic aberrations which affect cellular homoeostasis and may result in disease. This literature review examines the current evidence for the role of oxidative stress in important ocular diseases with a view to identifying potential therapeutic targets for future study. The need is particularly pressing in developing treatments for conditions which remain notoriously difficult to treat, including glaucoma, diabetic retinopathy and age-related macular degeneration.

scholarly journals Calcineurin Activation by Prion Protein Induces Neurotoxicity via Mitochondrial Reactive Oxygen Species

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Ji-Hong Moon ◽  
Jeong-Min Hong ◽  
Sang-Youel Park
Keyword(s):  
Reactive Oxygen Species ◽  
Prion Protein ◽  
Neuronal Apoptosis ◽  
Prion Diseases ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Cellular Functions ◽  
Mitochondrial Injury ◽  
The Brain

Prion diseases are caused by PrPsc accumulation in the brain, which triggers dysfunctional mitochondrial injury and reactive oxygen species (ROS) generation in neurons. Recent studies on prion diseases suggest that endoplasmic reticulum (ER) stress induced by misfolding proteins such as misfolded prion protein results in activation of calcineurin. Calcineurin is a calcium-related protein phosphatase of type 2B that exists in copious quantities in the brain and acts as a critical nodal component in the control of cellular functions. To investigate the relationship between calcineurin and intracellular ROS, we assessed the alteration of CaN and ROS induced by prion peptide (PrP) 106-126. Human prion peptide increased mitochondrial ROS by activating calcineurin, and the inhibition of calcineurin activity protected mitochondrial function and neuronal apoptosis in neuronal cells. These results suggest that calcineurin plays a pivotal role in neuronal apoptosis by mediating mitochondrial injury and ROS in prion diseases.

scholarly journals Differential expression pattern of genes involved in oxygen metabolism in epithelial oviductal cells during primary in vitro culture

2019 ◽  
Vol 7 (2) ◽  
pp. 66-76
Author(s):  
Katarzyna Stefańska ◽  
Sandra Knap ◽  
Magdalena Kulus ◽  
Ievgenia Kocherova ◽  
Piotr Celichowski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Epithelial Cells ◽  
In Vitro Culture ◽  
Cellular Response ◽  
Reactive Oxygen ◽  
Oxygen Metabolism ◽  
Female Reproductive Tract ◽  
Oxygen Species

AbstractOxygen metabolism is crucial in establishing successful pregnancy, since excessive amount of reactive oxygen species (ROS) may exert deleterious effects on the developing embryo. There are several defense mechanisms against oxidative stress in the female reproductive tract, including production of antioxidant enzymes by oviductal epithelial cells (OECs). Undoubtedly, OECs play major part in female fertility and may also serve as an in vitro model of the oviduct. Therefore, the aim of this study was to investigate the expression of genes involved in oxygen metabolism. We have isolated OECs from oviducts of crossbred gilts (n=45) and maintained their in vitro culture for 30 days, collecting their RNA at days 1, 7, 15 and 30. The gene expression was determined with the use of Affymetrix® Porcine Gene 1.1 ST Array Strip. Our results revealed 166 differentially expressed genes belonging to four ontology groups: „cellular response to oxidative stress”, “cellular response to oxygen-containing compound”, “cellular response to oxygen levels” and “cellular response to reactive oxygen species”, most of which are also involved in other major processes in the organism. However, our findings provide a valuable insight into porcine reproductive biology and may be utilized in optimization of assisted reproduction techniques.Running title: Genes involved in oxygen metabolism in oviductal epithelial cells

Clinical aspects of reactive oxygen and nitrogen species

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Tissue ◽  
Rapid Development ◽  
Reactive Oxygen ◽  
Clinical Aspects ◽  
No Production ◽  
Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

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