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http://hdl.handle.net/10662/21385
Títulos: | SARAF overexpression impairs thrombin‐induced Ca2+ homeostasis in neonatal platelets |
Autores/as: | Berna Erro, Alejandro Granados Conejero, María Purificación Teruel Montoya, Raúl Ferrer Marín, Francisca Delgado Casado, Elena Corbacho, Antonio Jesus Fernández, Esperanza Tapia García, José Antonio Cosme Redondo, Pedro |
Palabras clave: | Ca2+ homeostasis;Neonatal platelets;Pannexin1;PDCD61;ALG2;SARAF;TBHQ;Plaquetas neonatales |
Fecha de publicación: | 2023 |
Editor/a: | John Barrett |
Resumen: | Neonatal platelets present a reduced response to the platelet agonist, thrombin (Thr), thus resulting in a deficient Thr-induced aggregation. These alterations are more pronounced in premature newborns. Here, our aim was to uncover the causes underneath the impaired Ca2+ homeostasis described in neonatal platelets. Both Ca2+ mobilization and Ca2+ influx in response to Thr are decreased in neonatal platelets compared to maternal and control woman platelets. In neonatal platelets, we observed impaired Ca2+ mobilization in response to the PAR-1 agonist (SFLLRN) or by blocking SERCA3 function with tert-butylhydroquinone. Regarding SOCE, the STIM1 regulatory protein, SARAF, was found overexpressed in neonatal platelets, promoting an increase in STIM1/SARAF interaction even under resting conditions. Additionally, higher interaction between SARAF and PDCD61/ALG2 was also observed, reducing SARAF ubiquitination and prolonging its half-life. These results were reproduced by overexpressing SARAF in MEG01 and DAMI cells. Finally, we also observed that pannexin 1 permeability is enhanced in response to Thr in control woman and maternal platelets, but not in neonatal platelets, hence, leading to the deregulation of the Ca2+ entry found in neonatal platelets. Summarizing, we show that in neonatal platelets both Ca2+ accumulation in the intracellular stores and Threvoked Ca2+ entry through either capacitative channels or non-selective channels are altered in neonatal platelets, contributing to deregulated Ca2+ homeostasis in neonatal platelets and leading to the altered aggregation observed in these subjects. |
URI: | http://hdl.handle.net/10662/21385 |
ISSN: | 0007-1048 |
DOI: | 10.1111/bjh.19210 |
Colección: | DFSIO - Artículos PHYQOL - Artículos |
Archivos
Archivo | Descripción | Tamaño | Formato | |
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bjh_19210.pdf | 6,07 MB | Adobe PDF | Descargar |
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