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 50-300 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.