TY  - THES
A1  - Wagner, Leonard
T1  - Zinc homeostasis in megakaryocytes
T1  - Studien zur Expression und Regulation von Zink-Transportern in Megakaryozyten
N2  - Zinc is an essential trace element for all living organisms. In mammals, including humans and mice, it is required for normal growth, development, hematopoiesis and immune defense. This thesis investigates the influence of zinc on the development of megakaryocytes (MKs), the cells responsible for bone marrow-derived platelet production. Furthermore, a detailed analysis of the expression of zinc import and export transporters (Slc39a/Slc30a genes) is carried out, firstly over the course of MK differentiation and secondly dependent on extracellular zinc.
N2  - Zink ist ein für alle lebenden Organismen essentiell wichtiges Spurenelement. Bei Säugetieren, einschließlich Menschen und Mäusen, ist es für normales Wachstum, die normale Entwicklung, Hämatopoese und Immunantwort erforderlich. Diese Arbeit untersucht den Einfluss von Zink auf die Entwicklung von Megakaryozyten (MKs), derjenigen Zellen, welche für die Produktion der Thrombozyten im Knochenmark verantwortlich sind. Darüber hinaus wird eine detaillierte Analyse der Expression von Zinkimporttransportern und Zinkexporttransportern (Slc39a / Slc30a-Gene) durchgeführt, zum einen im Verlauf der MK-Differenzierung und zum anderen in Abhängigkeit von extrazellulärem Zink.
KW  - Zink
KW  - Megakaryozyt
KW  - Hämostase
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214526
ER  - 
TY  - JOUR
A1  - Gotru, Sanjeev Kiran
A1  - van Geffen, Johanna P.
A1  - Nagy, Magdolna
A1  - Mammadova-Bach, Elmina
A1  - Eilenberger, Julia
A1  - Volz, Julia
A1  - Manukjan, Georgi
A1  - Schulze, Harald
A1  - Wagner, Leonard
A1  - Eber, Stefan
A1  - Schambeck, Christian
A1  - Deppermann, Carsten
A1  - Brouns, Sanne
A1  - Nurden, Paquita
A1  - Greinacher, Andreas
A1  - Sachs, Ulrich
A1  - Nieswandt, Bernhard
A1  - Hermanns, Heike M.
A1  - Heemskerk, Johan W. M.
A1  - Braun, Attila
T1  - Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases
JF  - Scientific Reports
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.
KW  - coagulation system
KW  - metals
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227455
VL  - 9
ER  -