Post-Translational Deimination of Immunological and Metabolic Protein Markers in Plasma and Extracellular Vesicles of Naked Mole-Rat (Heterocephalus glaber)

Autor: Igor Kraev, Pinar Uysal-Onganer, Sigrun Lange, Matthew E. Pamenter, Kenny W. Huynh
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Protein moonlighting
Proteomics
naked mole-rat (heterocephalus glaber)
lcsh:Chemistry
chemistry.chemical_compound
peptidylarginine deiminases (PADs)
Plasma
0302 clinical medicine
Citrulline
Protein Interaction Maps
lcsh:QH301-705.5
Spectroscopy
Regulation of gene expression
0303 health sciences
education.field_of_study
Genome
biology
Citrullination
General Medicine
Blood Proteins
Blood proteins
3. Good health
Computer Science Applications
Cell biology
microRNA (miR21
miR155
miR210)
medicine.symptom
naked mole-rat (Heterocephalus glaber)
mir210)
Population
Longevity
Inflammation
Arginine
Catalysis
microrna (mir21
Article
Inorganic Chemistry
03 medical and health sciences
Extracellular Vesicles
medicine
mir155
Animals
Humans
Physical and Theoretical Chemistry
education
Molecular Biology
Naked mole-rat
030304 developmental biology
Mole Rats
Organic Chemistry
Immunity
biology.organism_classification
MicroRNAs
chemistry
lcsh:Biology (General)
lcsh:QD1-999
Gene Expression Regulation
Protein-Arginine Deiminases
protein deimination
extracellular vesicles (EVs)
metabolism
Protein Processing
Post-Translational
030217 neurology & neurosurgery
Biomarkers
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 20, Iss 21, p 5378 (2019)
Volume 20
Issue 21
ISSN: 1422-0067
Popis: Naked mole-rats are long-lived animals that show unusual resistance to hypoxia, cancer and ageing. Protein deimination is an irreversible post-translational modification caused by the peptidylarginine deiminase (PAD) family of enzymes, which convert arginine into citrulline in target proteins. Protein deimination can cause structural and functional protein changes, facilitating protein moonlighting, but also leading to neo-epitope generation and effects on gene regulation. Furthermore, PADs have been found to regulate cellular release of extracellular vesicles (EVs), which are lipid-vesicles released from cells as part of cellular communication. EVs carry protein and genetic cargo and are indicative biomarkers that can be isolated from most body fluids. This study was aimed at profiling deiminated proteins in plasma and EVs of naked mole-rat. Key immune and metabolic proteins were identified to be post-translationally deiminated, with 65 proteins specific for plasma, while 42 proteins were identified to be deiminated in EVs only. Using protein-protein interaction network analysis, deiminated plasma proteins were found to belong to KEEG (Kyoto Encyclopedia of Genes and Genomes) pathways of immunity, infection, cholesterol and drug metabolism, while deiminated proteins in EVs were also linked to KEEG pathways of HIF-1 signalling and glycolysis. The mole-rat EV profiles showed a poly-dispersed population of 50&ndash
300 nm, similar to observations of human plasma. Furthermore, the EVs were assessed for three key microRNAs involved in cancer, inflammation and hypoxia. The identification of post-translational deimination of critical immunological and metabolic markers contributes to the current understanding of protein moonlighting functions, via post-translational changes, in the longevity and cancer resistance of naked mole-rats.
Databáze: OpenAIRE
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