NAADP/SERCA3-Dependent Ca 2+ Stores Pathway Specifically Controls Early Autocrine ADP Secretion Potentiating Platelet Activation
| Autor: | Cécile V. Denis, Frédéric Adam, Delphine Borgel, Regis Bobe, Jean-Philippe Rosa, Ziane Elaib, Miao Feng, Marijke Bryckaert |
|---|---|
| Přispěvatelé: | 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 |
| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | Circulation Research Circulation Research, American Heart Association, 2020, 127 (7), pp.e166-e183. ⟨10.1161/CIRCRESAHA.119.316090⟩ |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/circresaha.119.316090 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|