Reciprocal modulation of surface expression of annexin A2 in a human umbilical vein endothelial cell-derived cell line by eicosapentaenoic acid and docosahexaenoic acid.

<h4>Background</h4>Annexin A2 (ANXA2), a member of the annexin family of cytosolic Ca(2+)-binding proteins, plays a pivotal role in vascular biology. Small amounts of this protein and S100A10 protein are exposed on the surface of endothelial cells (ECs). They control fibrinolysis by recr...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jungha Park, Takayuki Yamaura, Jun Kawamoto, Tatsuo Kurihara, Satoshi B Sato
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c5fffd528946470eaabd0c53fa60715d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c5fffd528946470eaabd0c53fa60715d
record_format	dspace
spelling	oai:doaj.org-article:c5fffd528946470eaabd0c53fa60715d2021-11-18T08:37:06ZReciprocal modulation of surface expression of annexin A2 in a human umbilical vein endothelial cell-derived cell line by eicosapentaenoic acid and docosahexaenoic acid.1932-620310.1371/journal.pone.0085045https://doaj.org/article/c5fffd528946470eaabd0c53fa60715d2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24465474/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Annexin A2 (ANXA2), a member of the annexin family of cytosolic Ca(2+)-binding proteins, plays a pivotal role in vascular biology. Small amounts of this protein and S100A10 protein are exposed on the surface of endothelial cells (ECs). They control fibrinolysis by recruiting tissue-type and urokinase-type plasminogen activators from the plasma. Nutritional studies indicate that two major long-chain polyunsaturated fatty acids (PUFAs), i.e., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), provide benefits for EC functions. The effects of EPA and DHA on the plasminogen/plasmin system have not been characterized.<h4>Methodology/principal findings</h4>Proteomic analysis of a cultured human umbilical vein EC-derived cell line, HUV-EC-C, showed that cell-associated ANXA2 decreased with EPA treatment and increased with DHA. A small fraction of ANXA2 was bound to the cell surface, which was also affected by these PUFAs following the same trends. Cell surface expression was negatively regulated by protein kinase C (PKC) α-mediated Ser-phosphorylation, which was up- and down-regulated by EPA and DHA, respectively. These PUFAs differentially affected a small fraction of caveolae/rafts-associated ANXA2. In addition to chymotrypsin-like activity in the serum, newly activated plasmin cleaved the ANXA2 on the cell surface at distinct sites in the N-terminal sequence. ANXA2 also bound to membranes released in the medium, which was similarly processed by these proteases. Both the PUFAs did not directly affect the release.<h4>Conclusion/significance</h4>These results suggest that EPA and DHA reciprocally control cell surface location of ANXA2. Moreover, cleavage of this protein by plasmin likely resulted in autodigestion of the platform for formation of this protease. In conjunction with termination of the proteolysis by rapid inactivation of plasmin by α-2-antiplasmin and other polypeptide inhibitors, this feedback mechanism may emphasize the benefits of these PUFA in regulation of the initiation of fibrinolysis on the surface of ECs.Jungha ParkTakayuki YamauraJun KawamotoTatsuo KuriharaSatoshi B SatoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e85045 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jungha Park Takayuki Yamaura Jun Kawamoto Tatsuo Kurihara Satoshi B Sato Reciprocal modulation of surface expression of annexin A2 in a human umbilical vein endothelial cell-derived cell line by eicosapentaenoic acid and docosahexaenoic acid.
description	<h4>Background</h4>Annexin A2 (ANXA2), a member of the annexin family of cytosolic Ca(2+)-binding proteins, plays a pivotal role in vascular biology. Small amounts of this protein and S100A10 protein are exposed on the surface of endothelial cells (ECs). They control fibrinolysis by recruiting tissue-type and urokinase-type plasminogen activators from the plasma. Nutritional studies indicate that two major long-chain polyunsaturated fatty acids (PUFAs), i.e., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), provide benefits for EC functions. The effects of EPA and DHA on the plasminogen/plasmin system have not been characterized.<h4>Methodology/principal findings</h4>Proteomic analysis of a cultured human umbilical vein EC-derived cell line, HUV-EC-C, showed that cell-associated ANXA2 decreased with EPA treatment and increased with DHA. A small fraction of ANXA2 was bound to the cell surface, which was also affected by these PUFAs following the same trends. Cell surface expression was negatively regulated by protein kinase C (PKC) α-mediated Ser-phosphorylation, which was up- and down-regulated by EPA and DHA, respectively. These PUFAs differentially affected a small fraction of caveolae/rafts-associated ANXA2. In addition to chymotrypsin-like activity in the serum, newly activated plasmin cleaved the ANXA2 on the cell surface at distinct sites in the N-terminal sequence. ANXA2 also bound to membranes released in the medium, which was similarly processed by these proteases. Both the PUFAs did not directly affect the release.<h4>Conclusion/significance</h4>These results suggest that EPA and DHA reciprocally control cell surface location of ANXA2. Moreover, cleavage of this protein by plasmin likely resulted in autodigestion of the platform for formation of this protease. In conjunction with termination of the proteolysis by rapid inactivation of plasmin by α-2-antiplasmin and other polypeptide inhibitors, this feedback mechanism may emphasize the benefits of these PUFA in regulation of the initiation of fibrinolysis on the surface of ECs.
format	article
author	Jungha Park Takayuki Yamaura Jun Kawamoto Tatsuo Kurihara Satoshi B Sato
author_facet	Jungha Park Takayuki Yamaura Jun Kawamoto Tatsuo Kurihara Satoshi B Sato
author_sort	Jungha Park
title	Reciprocal modulation of surface expression of annexin A2 in a human umbilical vein endothelial cell-derived cell line by eicosapentaenoic acid and docosahexaenoic acid.
title_short	Reciprocal modulation of surface expression of annexin A2 in a human umbilical vein endothelial cell-derived cell line by eicosapentaenoic acid and docosahexaenoic acid.
title_full	Reciprocal modulation of surface expression of annexin A2 in a human umbilical vein endothelial cell-derived cell line by eicosapentaenoic acid and docosahexaenoic acid.
title_fullStr	Reciprocal modulation of surface expression of annexin A2 in a human umbilical vein endothelial cell-derived cell line by eicosapentaenoic acid and docosahexaenoic acid.
title_full_unstemmed	Reciprocal modulation of surface expression of annexin A2 in a human umbilical vein endothelial cell-derived cell line by eicosapentaenoic acid and docosahexaenoic acid.
title_sort	reciprocal modulation of surface expression of annexin a2 in a human umbilical vein endothelial cell-derived cell line by eicosapentaenoic acid and docosahexaenoic acid.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/c5fffd528946470eaabd0c53fa60715d
work_keys_str_mv	AT junghapark reciprocalmodulationofsurfaceexpressionofannexina2inahumanumbilicalveinendothelialcellderivedcelllinebyeicosapentaenoicacidanddocosahexaenoicacid AT takayukiyamaura reciprocalmodulationofsurfaceexpressionofannexina2inahumanumbilicalveinendothelialcellderivedcelllinebyeicosapentaenoicacidanddocosahexaenoicacid AT junkawamoto reciprocalmodulationofsurfaceexpressionofannexina2inahumanumbilicalveinendothelialcellderivedcelllinebyeicosapentaenoicacidanddocosahexaenoicacid AT tatsuokurihara reciprocalmodulationofsurfaceexpressionofannexina2inahumanumbilicalveinendothelialcellderivedcelllinebyeicosapentaenoicacidanddocosahexaenoicacid AT satoshibsato reciprocalmodulationofsurfaceexpressionofannexina2inahumanumbilicalveinendothelialcellderivedcelllinebyeicosapentaenoicacidanddocosahexaenoicacid
_version_	1718421586611011584

Reciprocal modulation of surface expression of annexin A2 in a human umbilical vein endothelial cell-derived cell line by eicosapentaenoic acid and docosahexaenoic acid.

Ejemplares similares