| Autor: |
Berna‐Erro, Alejandro, Granados, Maria P., Teruel‐Montoya, Raul, Ferrer‐Marin, Francisca, Delgado, Elena, Corbacho, Antonio J., Fenández, Esperanza, Vazquez‐Godoy, Maria T., Tapia, Jose A., Redondo, Pedro Cosme |
| Předmět: |
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| Zdroj: |
British Journal of Haematology; Mar2024, Vol. 204 Issue 3, p988-1004, 17p |
| Abstrakt: |
Summary: 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 Thr‐evoked 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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