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Post-Translational Protein Deimination Signatures in Plasma and Plasma EVs of Reindeer (Rangifer tarandus)

SIMPLE SUMMARY: Reindeer are an important wild and domesticated species of the Arctic, Northern Europe, Siberia and North America. As reindeer have developed various strategies to adapt to extreme environments, this makes them an interesting species for studies into diversity of immune and metabolic...

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Autores principales: D’Alessio, Stefania, Thorgeirsdóttir, Stefanía, Kraev, Igor, Skírnisson, Karl, Lange, Sigrun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998281/
https://www.ncbi.nlm.nih.gov/pubmed/33805829
http://dx.doi.org/10.3390/biology10030222
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author D’Alessio, Stefania
Thorgeirsdóttir, Stefanía
Kraev, Igor
Skírnisson, Karl
Lange, Sigrun
author_facet D’Alessio, Stefania
Thorgeirsdóttir, Stefanía
Kraev, Igor
Skírnisson, Karl
Lange, Sigrun
author_sort D’Alessio, Stefania
collection PubMed
description SIMPLE SUMMARY: Reindeer are an important wild and domesticated species of the Arctic, Northern Europe, Siberia and North America. As reindeer have developed various strategies to adapt to extreme environments, this makes them an interesting species for studies into diversity of immune and metabolic functions in the animal kingdom. Importantly, while reindeer carry natural infections caused by viruses (including coronaviruses), bacteria and parasites, they can also act as carriers for transmitting such diseases to other animals and humans, so called zoonosis. Reindeer are also affected by chronic wasting disease, a neuronal disease caused by prions, similar to scrapie in sheep, mad cows disease in cattle and Creutzfeldt-Jakob disease in humans. The current study assessed a specific protein modification called deimination/citrullination, which can change how proteins function and allow them to take on different roles in health and disease processes. Profiling of deiminated proteins in reindeer showed that many important pathways for immune defenses, prion diseases and metabolism are enriched in deiminated proteins, both in plasma, as well as in plasma extracellular vesicles. This study provides a platform for the development of novel biomarkers to assess wild life health status and factors relating to zoonotic disease. ABSTRACT: The reindeer (caribou) Rangifer tarandus is a Cervidae in the order Artiodactyla. Reindeer are sedentary and migratory populations with circumpolar distribution in the Arctic, Northern Europe, Siberia and North America. Reindeer are an important wild and domesticated species, and have developed various adaptive strategies to extreme environments. Importantly, deer have also been identified to be putative zoonotic carriers, including for parasites, prions and coronavirus. Therefore, novel insights into immune-related markers are of considerable interest. Peptidylarginine deiminases (PADs) are a phylogenetically conserved enzyme family which causes post-translational protein deimination by converting arginine into citrulline in target proteins. This affects protein function in health and disease. Extracellular vesicles (EVs) participate in cellular communication, in physiological and pathological processes, via transfer of cargo material, and their release is partly regulated by PADs. This study assessed deiminated protein and EV profile signatures in plasma from sixteen healthy wild female reindeer, collected in Iceland during screening for parasites and chronic wasting disease. Reindeer plasma EV profiles showed a poly-dispersed distribution from 30 to 400 nm and were positive for phylogenetically conserved EV-specific markers. Deiminated proteins were isolated from whole plasma and plasma EVs, identified by proteomic analysis and protein interaction networks assessed by KEGG and GO analysis. This revealed a large number of deimination-enriched pathways for immunity and metabolism, with some differences between whole plasma and EVs. While shared KEGG pathways for whole plasma and plasma EVs included complement and coagulation pathways, KEGG pathways specific for EVs were for protein digestion and absorption, platelet activation, amoebiasis, the AGE–RAGE signaling pathway in diabetic complications, ECM receptor interaction, the relaxin signaling pathway and the estrogen signaling pathway. KEGG pathways specific for whole plasma were pertussis, ferroptosis, SLE, thyroid hormone synthesis, phagosome, Staphylococcus aureus infection, vitamin digestion and absorption, and prion disease. Further differences were also found between molecular function and biological processes GO pathways when comparing functional STRING networks for deiminated proteins in EVs, compared with deiminated proteins in whole plasma. This study highlights deiminated proteins and EVs as candidate biomarkers for reindeer health and may provide information on regulation of immune pathways in physiological and pathological processes, including neurodegenerative (prion) disease and zoonosis.
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spelling pubmed-79982812021-03-28 Post-Translational Protein Deimination Signatures in Plasma and Plasma EVs of Reindeer (Rangifer tarandus) D’Alessio, Stefania Thorgeirsdóttir, Stefanía Kraev, Igor Skírnisson, Karl Lange, Sigrun Biology (Basel) Article SIMPLE SUMMARY: Reindeer are an important wild and domesticated species of the Arctic, Northern Europe, Siberia and North America. As reindeer have developed various strategies to adapt to extreme environments, this makes them an interesting species for studies into diversity of immune and metabolic functions in the animal kingdom. Importantly, while reindeer carry natural infections caused by viruses (including coronaviruses), bacteria and parasites, they can also act as carriers for transmitting such diseases to other animals and humans, so called zoonosis. Reindeer are also affected by chronic wasting disease, a neuronal disease caused by prions, similar to scrapie in sheep, mad cows disease in cattle and Creutzfeldt-Jakob disease in humans. The current study assessed a specific protein modification called deimination/citrullination, which can change how proteins function and allow them to take on different roles in health and disease processes. Profiling of deiminated proteins in reindeer showed that many important pathways for immune defenses, prion diseases and metabolism are enriched in deiminated proteins, both in plasma, as well as in plasma extracellular vesicles. This study provides a platform for the development of novel biomarkers to assess wild life health status and factors relating to zoonotic disease. ABSTRACT: The reindeer (caribou) Rangifer tarandus is a Cervidae in the order Artiodactyla. Reindeer are sedentary and migratory populations with circumpolar distribution in the Arctic, Northern Europe, Siberia and North America. Reindeer are an important wild and domesticated species, and have developed various adaptive strategies to extreme environments. Importantly, deer have also been identified to be putative zoonotic carriers, including for parasites, prions and coronavirus. Therefore, novel insights into immune-related markers are of considerable interest. Peptidylarginine deiminases (PADs) are a phylogenetically conserved enzyme family which causes post-translational protein deimination by converting arginine into citrulline in target proteins. This affects protein function in health and disease. Extracellular vesicles (EVs) participate in cellular communication, in physiological and pathological processes, via transfer of cargo material, and their release is partly regulated by PADs. This study assessed deiminated protein and EV profile signatures in plasma from sixteen healthy wild female reindeer, collected in Iceland during screening for parasites and chronic wasting disease. Reindeer plasma EV profiles showed a poly-dispersed distribution from 30 to 400 nm and were positive for phylogenetically conserved EV-specific markers. Deiminated proteins were isolated from whole plasma and plasma EVs, identified by proteomic analysis and protein interaction networks assessed by KEGG and GO analysis. This revealed a large number of deimination-enriched pathways for immunity and metabolism, with some differences between whole plasma and EVs. While shared KEGG pathways for whole plasma and plasma EVs included complement and coagulation pathways, KEGG pathways specific for EVs were for protein digestion and absorption, platelet activation, amoebiasis, the AGE–RAGE signaling pathway in diabetic complications, ECM receptor interaction, the relaxin signaling pathway and the estrogen signaling pathway. KEGG pathways specific for whole plasma were pertussis, ferroptosis, SLE, thyroid hormone synthesis, phagosome, Staphylococcus aureus infection, vitamin digestion and absorption, and prion disease. Further differences were also found between molecular function and biological processes GO pathways when comparing functional STRING networks for deiminated proteins in EVs, compared with deiminated proteins in whole plasma. This study highlights deiminated proteins and EVs as candidate biomarkers for reindeer health and may provide information on regulation of immune pathways in physiological and pathological processes, including neurodegenerative (prion) disease and zoonosis. MDPI 2021-03-13 /pmc/articles/PMC7998281/ /pubmed/33805829 http://dx.doi.org/10.3390/biology10030222 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
D’Alessio, Stefania
Thorgeirsdóttir, Stefanía
Kraev, Igor
Skírnisson, Karl
Lange, Sigrun
Post-Translational Protein Deimination Signatures in Plasma and Plasma EVs of Reindeer (Rangifer tarandus)
title Post-Translational Protein Deimination Signatures in Plasma and Plasma EVs of Reindeer (Rangifer tarandus)
title_full Post-Translational Protein Deimination Signatures in Plasma and Plasma EVs of Reindeer (Rangifer tarandus)
title_fullStr Post-Translational Protein Deimination Signatures in Plasma and Plasma EVs of Reindeer (Rangifer tarandus)
title_full_unstemmed Post-Translational Protein Deimination Signatures in Plasma and Plasma EVs of Reindeer (Rangifer tarandus)
title_short Post-Translational Protein Deimination Signatures in Plasma and Plasma EVs of Reindeer (Rangifer tarandus)
title_sort post-translational protein deimination signatures in plasma and plasma evs of reindeer (rangifer tarandus)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998281/
https://www.ncbi.nlm.nih.gov/pubmed/33805829
http://dx.doi.org/10.3390/biology10030222
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