Cyclophilin A Is Not Acetylated at Lysine-82 and Lysine-125 in Resting and Stimulated Platelets
Cyclophilin A (CyPA) is widely expressed by all prokaryotic and eukaryotic cells. Upon activation, CyPA can be released into the extracellular space to engage in a variety of functions, such as interaction with the CD147 receptor, that contribute to the pathogenesis of cardiovascular diseases. CyPA...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836233/ https://www.ncbi.nlm.nih.gov/pubmed/35163387 http://dx.doi.org/10.3390/ijms23031469 |
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author | Rosa, Annabelle Butt, Elke Hopper, Christopher P. Loroch, Stefan Bender, Markus Schulze, Harald Sickmann, Albert Vorlova, Sandra Seizer, Peter Heinzmann, David Zernecke, Alma |
author_facet | Rosa, Annabelle Butt, Elke Hopper, Christopher P. Loroch, Stefan Bender, Markus Schulze, Harald Sickmann, Albert Vorlova, Sandra Seizer, Peter Heinzmann, David Zernecke, Alma |
author_sort | Rosa, Annabelle |
collection | PubMed |
description | Cyclophilin A (CyPA) is widely expressed by all prokaryotic and eukaryotic cells. Upon activation, CyPA can be released into the extracellular space to engage in a variety of functions, such as interaction with the CD147 receptor, that contribute to the pathogenesis of cardiovascular diseases. CyPA was recently found to undergo acetylation at K82 and K125, two lysine residues conserved in most species, and these modifications are required for secretion of CyPA in response to cell activation in vascular smooth muscle cells. Herein we addressed whether acetylation at these sites is also required for the release of CyPA from platelets based on the potential for local delivery of CyPA that may exacerbate cardiovascular disease events. Western blot analyses confirmed the presence of CyPA in human and mouse platelets. Thrombin stimulation resulted in CyPA release from platelets; however, no acetylation was observed—neither in cell lysates nor in supernatants of both untreated and activated platelets, nor after immunoprecipitation of CyPA from platelets. Shotgun proteomics detected two CyPA peptide precursors in the recombinant protein, acetylated at K28, but again, no acetylation was found in CyPA derived from resting or stimulated platelets. Our findings suggest that acetylation of CyPA is not a major protein modification in platelets and that CyPA acetylation is not required for its secretion from platelets. |
format | Online Article Text |
id | pubmed-8836233 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88362332022-02-12 Cyclophilin A Is Not Acetylated at Lysine-82 and Lysine-125 in Resting and Stimulated Platelets Rosa, Annabelle Butt, Elke Hopper, Christopher P. Loroch, Stefan Bender, Markus Schulze, Harald Sickmann, Albert Vorlova, Sandra Seizer, Peter Heinzmann, David Zernecke, Alma Int J Mol Sci Article Cyclophilin A (CyPA) is widely expressed by all prokaryotic and eukaryotic cells. Upon activation, CyPA can be released into the extracellular space to engage in a variety of functions, such as interaction with the CD147 receptor, that contribute to the pathogenesis of cardiovascular diseases. CyPA was recently found to undergo acetylation at K82 and K125, two lysine residues conserved in most species, and these modifications are required for secretion of CyPA in response to cell activation in vascular smooth muscle cells. Herein we addressed whether acetylation at these sites is also required for the release of CyPA from platelets based on the potential for local delivery of CyPA that may exacerbate cardiovascular disease events. Western blot analyses confirmed the presence of CyPA in human and mouse platelets. Thrombin stimulation resulted in CyPA release from platelets; however, no acetylation was observed—neither in cell lysates nor in supernatants of both untreated and activated platelets, nor after immunoprecipitation of CyPA from platelets. Shotgun proteomics detected two CyPA peptide precursors in the recombinant protein, acetylated at K28, but again, no acetylation was found in CyPA derived from resting or stimulated platelets. Our findings suggest that acetylation of CyPA is not a major protein modification in platelets and that CyPA acetylation is not required for its secretion from platelets. MDPI 2022-01-27 /pmc/articles/PMC8836233/ /pubmed/35163387 http://dx.doi.org/10.3390/ijms23031469 Text en © 2022 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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rosa, Annabelle Butt, Elke Hopper, Christopher P. Loroch, Stefan Bender, Markus Schulze, Harald Sickmann, Albert Vorlova, Sandra Seizer, Peter Heinzmann, David Zernecke, Alma Cyclophilin A Is Not Acetylated at Lysine-82 and Lysine-125 in Resting and Stimulated Platelets |
title | Cyclophilin A Is Not Acetylated at Lysine-82 and Lysine-125 in Resting and Stimulated Platelets |
title_full | Cyclophilin A Is Not Acetylated at Lysine-82 and Lysine-125 in Resting and Stimulated Platelets |
title_fullStr | Cyclophilin A Is Not Acetylated at Lysine-82 and Lysine-125 in Resting and Stimulated Platelets |
title_full_unstemmed | Cyclophilin A Is Not Acetylated at Lysine-82 and Lysine-125 in Resting and Stimulated Platelets |
title_short | Cyclophilin A Is Not Acetylated at Lysine-82 and Lysine-125 in Resting and Stimulated Platelets |
title_sort | cyclophilin a is not acetylated at lysine-82 and lysine-125 in resting and stimulated platelets |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836233/ https://www.ncbi.nlm.nih.gov/pubmed/35163387 http://dx.doi.org/10.3390/ijms23031469 |
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