Platelets Selectively Regulate the Release of BDNF, But Not That of Its Precursor Protein, proBDNF
| Autor: | Marie Lordkipanidzé, Imane Boukhatem, Jessica Le Blanc, Jean-Christophe Bélanger, Samuel Fleury, Mélanie Welman |
|---|---|
| Přispěvatelé: | Université de Montréal. Faculté de pharmacie |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Blood Platelets Male lcsh:Immunologic diseases. Allergy medicine.medical_specialty Platelet Aggregation Immunology Stimulation Neuroprotection Flow cytometry 03 medical and health sciences Young Adult 0302 clinical medicine Neurotrophic factors Internal medicine medicine Immunology and Allergy Humans Platelet Platelet activation Protein Precursors pro-BDNF plasma Brain-derived neurotrophic factor Arachidonic Acid Secretory Pathway medicine.diagnostic_test Chemistry brain-derived neurotrophic factor Brief Research Report Middle Aged Platelet Activation Adenosine Diphosphate secretion 030104 developmental biology Endocrinology nervous system Synaptic plasticity platelets Female Collagen lcsh:RC581-607 030217 neurology & neurosurgery |
| Zdroj: | Frontiers in Immunology, Vol 11 (2020) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| Popis: | BackgroundBrain-derived neurotrophic factor (BDNF) plays a role in synaptic plasticity and neuroprotection. BDNF has well-established pro-survival effects, whereas its precursor protein, proBDNF, induces apoptosis. Thus, it has been suggested that the proBDNF/BDNF ratio could be an indicator of neuronal health. Access to neurons is, understandably, limited. Because of their similarities, platelets have been put forward as a non-invasive biomarker of neuronal health; indeed, they store large quantities of BDNF and can release it into circulation upon activation, similarly to neurons. However, whether platelets also express the precursor proBDNF protein remains unknown. We therefore sought to characterize proBDNF levels in human platelets and plasma.MethodsThe presence of proBDNF was assessed by immunoblotting, cell fractionation, flow cytometry, and confocal microscopy in washed platelets from 10 healthy volunteers. Platelets from 20 independent healthy volunteers were activated with several classical agonists and the release of BDNF and proBDNF into plasma was quantified by ELISA.ResultsPlatelets expressed detectable levels of proBDNF (21 ± 13 fmol/250 x 106 platelets). ProBDNF expression was mainly localized in the intracellular compartment. The proBDNF to BDNF molar ratio was ~1:5 in platelets and 10:1 in plasma. In stark contrast to the release of BDNF during platelet activation, intraplatelet and plasma concentrations of proBDNF remained stable following stimulation with classical platelet agonists, consistent with non-granular expression.ConclusionsPlatelets express both the mature and the precursor form of BDNF. Whether the intraplatelet proBDNF to BDNF ratio could be used as a non-invasive biomarker of cognitive health warrants further investigation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|