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Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases

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Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases. / Kiran Gotru, Sanjeev; van Geffen, Johanna P; Nagy, Magdolna; Mammadova-Bach, Elmina; Eilenberger, Julia; Volz, Julia; Manukjan, Georgi; Schulze, Harald; Wagner, Leonard; Eber, Stefan; Schambeck, Christian; Deppermann, Carsten; Brouns, Sanne; Nurden, Paquita; Greinacher, Andreas; Sachs, Ulrich; Nieswandt, Bernhard; Hermanns, Heike M; Heemskerk, Johan W M; Braun, Attila.

In: SCI REP-UK, Vol. 9, No. 1, 06.06.2019, p. 8333.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Kiran Gotru, S, van Geffen, JP, Nagy, M, Mammadova-Bach, E, Eilenberger, J, Volz, J, Manukjan, G, Schulze, H, Wagner, L, Eber, S, Schambeck, C, Deppermann, C, Brouns, S, Nurden, P, Greinacher, A, Sachs, U, Nieswandt, B, Hermanns, HM, Heemskerk, JWM & Braun, A 2019, 'Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases', SCI REP-UK, vol. 9, no. 1, pp. 8333. https://doi.org/10.1038/s41598-019-44751-w

APA

Kiran Gotru, S., van Geffen, J. P., Nagy, M., Mammadova-Bach, E., Eilenberger, J., Volz, J., Manukjan, G., Schulze, H., Wagner, L., Eber, S., Schambeck, C., Deppermann, C., Brouns, S., Nurden, P., Greinacher, A., Sachs, U., Nieswandt, B., Hermanns, H. M., Heemskerk, J. W. M., & Braun, A. (2019). Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases. SCI REP-UK, 9(1), 8333. https://doi.org/10.1038/s41598-019-44751-w

Vancouver

Kiran Gotru S, van Geffen JP, Nagy M, Mammadova-Bach E, Eilenberger J, Volz J et al. Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases. SCI REP-UK. 2019 Jun 6;9(1):8333. https://doi.org/10.1038/s41598-019-44751-w

Bibtex

@article{3f91f085a2d3467f9bb81524c3c44d83,
title = "Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases",
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.",
author = "{Kiran Gotru}, Sanjeev and {van Geffen}, {Johanna P} and Magdolna Nagy and Elmina Mammadova-Bach and Julia Eilenberger and Julia Volz and Georgi Manukjan and Harald Schulze and Leonard Wagner and Stefan Eber and Christian Schambeck and Carsten Deppermann and Sanne Brouns and Paquita Nurden and Andreas Greinacher and Ulrich Sachs and Bernhard Nieswandt and Hermanns, {Heike M} and Heemskerk, {Johan W M} and Attila Braun",
year = "2019",
month = jun,
day = "6",
doi = "10.1038/s41598-019-44751-w",
language = "English",
volume = "9",
pages = "8333",
journal = "SCI REP-UK",
issn = "2045-2322",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases

AU - Kiran Gotru, Sanjeev

AU - van Geffen, Johanna P

AU - Nagy, Magdolna

AU - Mammadova-Bach, Elmina

AU - Eilenberger, Julia

AU - Volz, Julia

AU - Manukjan, Georgi

AU - Schulze, Harald

AU - Wagner, Leonard

AU - Eber, Stefan

AU - Schambeck, Christian

AU - Deppermann, Carsten

AU - Brouns, Sanne

AU - Nurden, Paquita

AU - Greinacher, Andreas

AU - Sachs, Ulrich

AU - Nieswandt, Bernhard

AU - Hermanns, Heike M

AU - Heemskerk, Johan W M

AU - Braun, Attila

PY - 2019/6/6

Y1 - 2019/6/6

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-019-44751-w

DO - 10.1038/s41598-019-44751-w

M3 - SCORING: Journal article

C2 - 31171812

VL - 9

SP - 8333

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

IS - 1

ER -