NAADP/SERCA3-Dependent Ca 2+ Stores Pathway Specifically Controls Early Autocrine ADP Secretion Potentiating Platelet Activation
| العنوان: | NAADP/SERCA3-Dependent Ca 2+ Stores Pathway Specifically Controls Early Autocrine ADP Secretion Potentiating Platelet Activation |
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| المؤلفون: | Cécile V. Denis, Frédéric Adam, Delphine Borgel, Regis Bobe, Jean-Philippe Rosa, Ziane Elaib, Miao Feng, Marijke Bryckaert |
| المساهمون: | Hémostase, Inflammation, Thrombose (HITH - U1176 Inserm - CHU Bicêtre), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, BOBE, Regis |
| المصدر: | Circulation Research Circulation Research, American Heart Association, 2020, 127 (7), pp.e166-e183. ⟨10.1161/CIRCRESAHA.119.316090⟩ |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Physiology, Chemistry, [SDV]Life Sciences [q-bio], Endoplasmic reticulum, Cell, 030204 cardiovascular system & hematology, Adenosine, sarcoplasmic reticulum, Cell biology, [SDV] Life Sciences [q-bio], endoplasmic reticulum, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, adenosine, platelet activation, medicine, Secretion, Platelet activation, Cardiology and Cardiovascular Medicine, Autocrine signalling, Reticulum, medicine.drug |
| الوصف: | Rationale: Ca 2+ signaling is a key and ubiquitous actor of cell organization and its modulation controls many cellular responses. SERCAs (sarco-endoplasmic reticulum Ca 2+ -ATPases) pump Ca 2+ into internal stores that play a major role in the cytosolic Ca 2+ concentration rise upon cell activation. Platelets exhibit 2 types of SERCAs, SERCA2b and SERCA3 (SERCA3 deficient mice), which may exert specific roles, yet ill-defined. We have recently shown that Ca 2+ mobilization from SERCA3-dependent stores was required for full platelet activation in weak stimulation conditions. Objective: To uncover the signaling mechanisms associated with Ca 2+ mobilization from SERCA3-dependent stores leading to ADP secretion. Methods and Results: Using platelets from wild-type or Serca3 -deficient mice, we demonstrated that an early (within 5–10 s following stimulation) secretion of ADP specifically dependent on SERCA3 stored Ca 2+ is exclusively mobilized by nicotinic acid adenosine dinucleotide-phosphate (NAADP): both Ca 2+ mobilization from SERCA3-dependent stores and primary ADP secretion are blocked by the NAADP receptor antagonist Ned-19, and reciprocally both are stimulated by permeant NAADP. In contrast, Ca 2+ mobilization from SERCA3-dependent stores and primary ADP secretion were unaffected by inhibition of the production of IP3 (inositol-1,4,5-trisphosphate) by phospholipase-C and accordingly were not stimulated by permeant IP3. Conclusions: Upon activation, an NAADP/SERCA3 Ca 2+ mobilization pathway initiates an early ADP secretion, potentiating platelet activation, and a secondary wave of ADP secretion driven by both an IP3/SERCA2b-dependent Ca 2+ stores pathway and the NAADP/SERCA3 pathway. This does not exclude that Ca 2+ mobilized from SERCA3 stores may also enhance platelet global reactivity to agonists. Because of its modulating effect on platelet activation, this NAADP-SERCA3 pathway may be a relevant target for anti-thrombotic therapy. Graphic Abstract: A graphic abstract is available for this article. |
| وصف الملف: | application/pdf |
| تدمد: | 1524-4571 0009-7330 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c54e26d94be7dc042d9ca3cb699d0d2cTest https://doi.org/10.1161/circresaha.119.316090Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c54e26d94be7dc042d9ca3cb699d0d2c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244571 00097330 |
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