Back to Search
Start Over
Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases
- Source :
- Scientific Reports, Vol 9, Iss 1, Pp 1-7 (2019), Scientific Reports, 9:8333. Nature Publishing Group
- Publication Year :
- 2019
-
Abstract
- Zinc (Zn2+) can modulate platelet and coagulation activation pathways, including fibrin formation. Here, we studied the (patho)physiological consequences of abnormal platelet Zn2+ storage and release. To visualize Zn2+ storage in human and mouse platelets, the Zn2+ specific fluorescent dye FluoZin3 was used. In resting platelets, the dye transiently accumulated into distinct cytosolic puncta, which were lost upon platelet activation. Platelets isolated from Unc13d−/− mice, characterized by combined defects of α/δ granular release, showed a markedly impaired Zn2+ release upon activation. Platelets from Nbeal2−/− mice mimicking Gray platelet syndrome (GPS), characterized by primarily loss of the α-granule content, had strongly reduced Zn2+ levels, which was also confirmed in primary megakaryocytes. In human platelets isolated from patients with GPS, Hermansky-Pudlak Syndrome (HPS) and Storage Pool Disease (SPD) altered Zn2+ homeostasis was detected. In turbidity and flow based assays, platelet-dependent fibrin formation was impaired in both Nbeal2−/− and Unc13d−/− mice, and the impairment could be partially restored by extracellular Zn2+. Altogether, we conclude that the release of ionic Zn2+ store from secretory granules upon platelet activation contributes to the procoagulant role of Zn2+ in platelet-dependent fibrin formation.
- Subjects :
- 0301 basic medicine
inorganic chemicals
lcsh:Medicine
NBEAL2
Fibrin
Gray platelet syndrome
ACTIVATION
03 medical and health sciences
ZINC
0302 clinical medicine
medicine
Extracellular
Platelet
HEMOSTASIS
Platelet activation
lcsh:Science
Abnormal Platelet
Multidisciplinary
ROLES
biology
PLASMA
Chemistry
METALLOTHIONEIN
lcsh:R
medicine.disease
Cell biology
030104 developmental biology
Coagulation
biological sciences
biology.protein
health occupations
bacteria
SECRETION
lcsh:Q
030217 neurology & neurosurgery
Homeostasis
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....1dc4ce1910fb62a082c0b9a4f5987eda