scholarly journals Fibrinogen-cellular prion protein complex formation on astrocytes

2020 ◽  
Vol 124 (2) ◽  
pp. 536-543 ◽  
Author(s):  
Mariam Charkviani ◽  
Nino Muradashvili ◽  
Nurul Sulimai ◽  
David Lominadze
Keyword(s):  
Prion Protein ◽  
Cellular Prion Protein ◽  
No Production ◽  
Oxygen Species ◽  
Receptor Kinase ◽  
Astrocyte Activation ◽  
Triggering Mechanism ◽  
Protein Complex Formation ◽  
Tyrosine Receptor Kinase ◽  
First Time

For the first time we showed that fibrinogen (Fg) can associate with cellular prion protein (PrPC) on the surface of cultured mouse brain astrocytes. At high levels, Fg causes upregulation of astrocyte PrPC and astrocyte activation accompanied with overexpression of tyrosine receptor kinase B (TrkB), which results in nitric oxide (NO) production and generation of reactive oxygen species (ROS). Fg/PrPC interaction can be a triggering mechanism for TrkB-NO-ROS axis activation and the resultant astrocyte-mediated neurodegeneration.

scholarly journals PrP glycoforms are associated in a strain-specific ratio in native PrPSc

2005 ◽  
Vol 86 (9) ◽  
pp. 2635-2644 ◽  
Author(s):  
Azadeh Khalili-Shirazi ◽  
Linda Summers ◽  
Jacqueline Linehan ◽  
Gary Mallinson ◽  
David Anstee ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Prion Protein ◽  
Prion Disease ◽  
Prion Diseases ◽  
Cellular Prion Protein ◽  
Normal Brain ◽  
Western Blots ◽  
Prion Strains ◽  
Specific Manner ◽  
First Time

Prion diseases involve conversion of host-encoded cellular prion protein (PrPC) to a disease-related isoform (PrPSc). Using recombinant human β-PrP, a panel of monoclonal antibodies was produced that efficiently immunoprecipitated native PrPSc and recognized epitopes between residues 93–105, indicating for the first time that this region is exposed in both human vCJD and mouse RML prions. In contrast, monoclonal antibodies raised to human α-PrP were more efficient in immunoprecipitating PrPC than PrPSc, and some of them could also distinguish between different PrP glycoforms. Using these monoclonal antibodies, the physical association of PrP glycoforms was studied in normal brain and in the brains of humans and mice with prion disease. It was shown that while PrPC glycoforms can be selectively immunoprecipitated, the differentially glycosylated molecules of native PrPSc are closely associated and always immunoprecipitate together. Furthermore, the ratio of glycoforms comprising immunoprecipitated native PrPSc from diverse prion strains was similar to those observed on denaturing Western blots. These studies are consistent with the view that the proportion of each glycoform incorporated into PrPSc is probably controlled in a strain-specific manner and that each PrPSc particle contains a mixture of glycoforms.

scholarly journals Prion protein and its role in signal transduction

2013 ◽  
Vol 18 (2) ◽  
Author(s):  
Alessandro Didonna
Keyword(s):  
Signal Transduction ◽  
Prion Protein ◽  
Neurodegenerative Disorders ◽  
Physiological Function ◽  
Prion Diseases ◽  
Etiologic Agent ◽  
Cellular Prion Protein ◽  
Considerable Effort ◽  
Unique Nature ◽  
First Time

AbstractPrion diseases are a class of fatal neurodegenerative disorders that can be sporadic, genetic or iatrogenic. They are characterized by the unique nature of their etiologic agent: prions (PrPSc). A prion is an infectious protein with the ability to convert the host-encoded cellular prion protein (PrPC) into new prion molecules by acting as a template. Since Stanley B. Prusiner proposed the “protein-only” hypothesis for the first time, considerable effort has been put into defining the role played by PrPC in neurons. However, its physiological function remains unclear. This review summarizes the major findings that support the involvement of PrPC in signal transduction.

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 Molecular Detection of Cellular Prion Protein in Brain Tissues of Black Bengal Goats in Bangladesh

2015 ◽  
Vol 3 (2) ◽  
pp. 1-4
Author(s):  
Nasrin Sultana ◽  
Mohd Zahirul Islam Khan ◽  
Emdadul Haque Choudhury ◽  
Md Rafiqul Islam
Keyword(s):  
Prion Protein ◽  
Molecular Detection ◽  
Cellular Prion Protein ◽  
The Central Nervous System ◽  
Membrane Bound ◽  
Polymerase Chain ◽  
First Time ◽  
The Brain ◽  
Prp Gene ◽  
Brain Tissues

The cellular prion protein (PrPC) is a membrane-bound glycoprotein mainlypresent in the central nervous system which is necessary for the establishmentand further evolution of prion disease in human and animals. The aim of thepresent study was to investigate the PrPC protein in brain tissues of black Bengalgoat. Fifteen brain tissues were collected from different slaughter houses ofthree districts (Mymensingh, Manikgonj and Netrokona) of Bangladesh duringJanuary to February, 2011. The PrPC protein was detected in the brain tissuesof black Bengal goats using polymerase chain reaction. The result showed allpositive (100%) of the amplified samples. The standardized PCR could be usedfor detection of PrPC protein in different tissues of animals and humans.Sequencing of PrP gene in the black Bengal goats for the risk assessment ofscrapie is needed for further study. To our knowledge, detection of PrPC proteinin the brain tissues of indigenous goats is the first time in Bangladesh.

Prion processing: a double-edged sword?

2012 ◽  
Vol 40 (4) ◽  
pp. 735-738 ◽  
Author(s):  
Hilary E.M. McMahon
Keyword(s):  
Prion Protein ◽  
Cellular Prion Protein ◽  
Conversion Process ◽  
Oxygen Species ◽  
Amino Acid Residues ◽  
Prion Infection ◽  
C And N ◽  
The Subject ◽  
Prion Conversion ◽  
Disease Specific

The events leading to the degradation of the endogenous PrPC (normal cellular prion protein) have been the subject of numerous studies. Two cleavage processes, α-cleavage and β-cleavage, are responsible for the main C- and N-terminal fragments produced from PrPC. Both cleavage processes occur within the N-terminus of PrPC, a region that is significant in terms of function. α-Cleavage, an enzymatic event that occurs at amino acid residues 110 and 111 on PrPC, interferes with the conversion of PrPC into the prion disease-associated isoform, PrPSc (abnormal disease-specific conformation of prion protein). This processing is seen as a positive event in terms of disease development. The study of β-cleavage has taken some surprising turns. β-Cleavage is brought about by ROS (reactive oxygen species). The C-terminal fragment produced, C2, may provide the seed for the abnormal conversion process, as it resembles in size the fragments isolated from prion-infected brains. There is, however, strong evidence that β-cleavage provides an essential process to reduce oxidative stress. β-Cleavage may act as a double-edged sword. By β-cleavage, PrPC may try to balance the ROS levels produced during prion infection, but the C2 produced may provide a PrPSc seed that maintains the prion conversion process.

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.

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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