Protein Deimination Signatures in Plasma and Plasma-EVs and Protein Deimination in the Brain Vasculature in a Rat Model of Pre-Motor Parkinson’s Disease

Autor: Igor Kraev, Marco Sancandi, Pinar Uysal-Onganer, Sigrun Lange, Audrey Mercer
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Proteomics
Parkinson's disease
Peptidylarginine deiminases (PADs)
Rats
Sprague-Dawley
lcsh:Chemistry
chemistry.chemical_compound
Tandem Mass Spectrometry
pre-motor Parkinson’s disease
Citrulline
Protein Interaction Maps
lcsh:QH301-705.5
Spectroscopy
Citrullination
Brain
Parkinson Disease
General Medicine
Extracellular vesicle
Endocannabinoid system
Immunohistochemistry
Computer Science Applications
Cell biology
Apelin
microRNA (miR21
miR155
miR210)
medicine.symptom
Inflammation
Biology
Catalysis
Article
Inorganic Chemistry
Extracellular Vesicles
Microscopy
Electron
Transmission
medicine
Animals
Platelet activation
Physical and Theoretical Chemistry
Molecular Biology
Organic Chemistry
medicine.disease
nervous system diseases
Rats
Disease Models
Animal
MicroRNAs
chemistry
lcsh:Biology (General)
lcsh:QD1-999
Protein-Arginine Deiminases
protein deimination
extracellular vesicles (EVs)
Protein Processing
Post-Translational
Biomarkers
Chromatography
Liquid
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 2743, p 2743 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 8
ISSN: 1661-6596
1422-0067
Popis: The identification of biomarkers for early diagnosis of Parkinson&rsquo
s disease (PD) is of pivotal importance for improving approaches for clinical intervention. The use of translatable animal models of pre-motor PD therefore offers optimal opportunities for novel biomarker discovery in vivo. Peptidylarginine deiminases (PADs) are a family of calcium-activated enzymes that contribute to protein misfolding through post-translational deimination of arginine to citrulline. Furthermore, PADs are an active regulator of extracellular vesicle (EV) release. Both protein deimination and extracellular vesicles (EVs) are gaining increased attention in relation to neurodegenerative diseases, including in PD, while roles in pre-motor PD have yet to be investigated. The current study aimed at identifying protein candidates of deimination in plasma and plasma-EVs in a rat model of pre-motor PD, to assess putative contributions of such post-translational changes in the early stages of disease. EV-cargo was further assessed for deiminated proteins as well as three key micro-RNAs known to contribute to inflammation and hypoxia (miR21, miR155, and miR210) and also associated with PD. Overall, there was a significant increase in circulating plasma EVs in the PD model compared with sham animals and inflammatory and hypoxia related microRNAs were significantly increased in plasma-EVs of the pre-motor PD model. A significantly higher number of protein candidates were deiminated in the pre-motor PD model plasma and plasma-EVs, compared with those in the sham animals. KEGG (Kyoto encyclopedia of genes and genomes) pathways identified for deiminated proteins in the pre-motor PD model were linked to &ldquo
Alzheimer&rsquo
s disease&rdquo
&ldquo
PD&rdquo
Huntington&rsquo
prion diseases&rdquo
as well as for &ldquo
oxidative phosphorylation&rdquo
thermogenesis&rdquo
metabolic pathways&rdquo
Staphylococcus aureus infection&rdquo
gap junction, &ldquo
platelet activation&rdquo
apelin signalling&rdquo
retrograde endocannabinoid signalling&rdquo
systemic lupus erythematosus&rdquo
and &ldquo
non-alcoholic fatty liver disease&rdquo
Furthermore, PD brains showed significantly increased staining for total deiminated proteins in the brain vasculature in cortex and hippocampus, as well as increased immunodetection of deiminated histone H3 in dentate gyrus and cortex. Our findings identify EVs and post-translational protein deimination as novel biomarkers in early pre-motor stages of PD.
Databáze: OpenAIRE
Externí odkaz: