scholarly journals Tauroursodeoxycholic Acid Protects against the Effects of P-Cresol-Induced Reactive Oxygen Species via the Expression of Cellular Prion Protein

2018 ◽  
Vol 19 (2) ◽  
pp. 352 ◽  
Author(s):  
Seung Yun ◽  
Yeo Yoon ◽  
Jun Lee ◽  
Minjee Kook ◽  
Yong-Seok Han ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Prion Protein ◽  
Reactive Oxygen ◽  
Cellular Prion Protein ◽  
Oxygen Species ◽  
Tauroursodeoxycholic Acid

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

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.

scholarly journals Pioglitazone Improves the Function of Human Mesenchymal Stem Cells in Chronic Kidney Disease Patients

2019 ◽  
Vol 20 (9) ◽  
pp. 2314 ◽  
Author(s):  
Yeo Min Yoon ◽  
Jun Hee Lee ◽  
Chul Won Yun ◽  
Sang Hun Lee
Keyword(s):  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Kidney Disease ◽  
Er Stress ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Cellular Prion Protein ◽  
Oxygen Species

Mesenchymal stem cells (MSCs) are optimal sources of autologous stem cells for cell-based therapy in chronic kidney disease (CKD). However, CKD-associated pathophysiological conditions, such as endoplasmic reticulum (ER) stress and oxidative stress, decrease MSC function. In this work, we study the protective effect of pioglitazone on MSCs isolated from CKD patients (CKD-MSCs) against CKD-induced ER stress. In CKD-MSCs, ER stress is found to induce mitochondrial reactive oxygen species generation and mitochondrial dysfunction. Treatment with pioglitazone reduces the expression of ER stress markers and mitochondrial fusion proteins. Pioglitazone increases the expression of cellular prion protein (PrPC) in CKD-MSCs, which is dependent on the expression levels of proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Treatment with pioglitazone is found to protect CKD-MSCs against reactive oxygen species generation, aberrant mitochondrial oxidative phosphorylation of complexes I and IV, and aberrant proliferation capacity through the PGC-1α-PrPC axis. These results indicate that pioglitazone protects the mitochondria of MSCs from CKD-induced ER stress. Pioglitazone treatment of CKD-MSCs may be a potential therapeutic strategy for CKD patients.

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 Cleavage of the Amino Terminus of the Prion Protein by Reactive Oxygen Species

2000 ◽  
Vol 276 (3) ◽  
pp. 2286-2291 ◽  
Author(s):  
Hilary E. M. McMahon ◽  
Alain Mangé ◽  
Noriyuki Nishida ◽  
Christophe Créminon ◽  
Danielle Casanova ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Prion Protein ◽  
Reactive Oxygen ◽  
Amino Terminus ◽  
Oxygen Species

Regulation of intrinsic prion protein by growth factors and tnf-α: the role of intracellular reactive oxygen species

2003 ◽  
Vol 35 (6) ◽  
pp. 586-594 ◽  
Author(s):  
Heinrich Sauer ◽  
Katrin Wefer ◽  
Vito Vetrugno ◽  
Maurizio Pocchiari ◽  
Cornelia Gissel ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Growth Factors ◽  
Prion Protein ◽  
Reactive Oxygen ◽  
Intracellular Reactive Oxygen Species ◽  
Oxygen Species ◽  
Tnf Α

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.

Mitochondria as a source of reactive oxygen species

2009 ◽  
pp. c3 ◽  
Author(s):  
Helena M. Cochemé ◽  
Michael P. Murphy
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species
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