Abstract/Details

Study of calcium transport processes in blood platelets using knock out mouse models. Regulation and role of “<i>store-operated calcium entry</i>” (SOCE)


2009 2009

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Abstract (summary)

Platelet activation and aggregation are essential to limit posttraumatic blood loss at sites of vascular injury but also contributes to arterial thrombosis, leading to myocardial infarction and stroke. Agonist-induced elevation of [Ca2+]i is a central step in platelet activation, but the underlying mechanisms are not fully understood. A major pathway for Ca2+-entry in non-excitable cells, such as platelets, involves receptor-mediated release of intracellular Ca2+ stores, followed by activation of store-operated calcium (SOC) channels in the plasma membrane.

In my PhD work I investigated the molecular background and the physiological relevance of store-operated calcium entry (SOCE) in platelets. I have identified stromal interaction molecule 1 (STIM1) and Orai1 to be the key components of SOCE in these cells, where STIM1 is the calcium sensor in the endoplasmic reticulum – the major calcium store – that upon store release signals to Orai1 – the major SOC channel in platelets – and open it to allow Ca2+-entry (Fig.34). Furthermore, I could exclude canonical transient receptor potential channel 1 (TRPC1) to have a major impact on this process. Using in vivo thrombosis models I could show that SOCE is of huge importance for stable thrombus formation under high shear flow conditions, such as found in diseased vessels, but lack of the process does not significantly increase bleeding risk. These latter findings establish platelet SOCE and the proteins involved in it as promising targets in the prevention and treatment of ischemic cardio- and cerebrovascular events.

Indexing (details)


Subject
Molecular biology;
Health sciences
Classification
0307: Molecular biology
0566: Health sciences
Identifier / keyword
Health and environmental sciences; Biological sciences; Blood platelets; Calcium transport; Store-operated calcium entry
Title
Study of calcium transport processes in blood platelets using knock out mouse models. Regulation and role of “<i>store-operated calcium entry</i>” (SOCE)
Author
Varga-Szabo, David
Number of pages
98
Publication year
2009
Degree date
2009
School code
1385
Source
DAI-B 71/08, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781124120256
University/institution
Semmelweis Egyetem (Hungary)
University location
Hungary
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3470354
ProQuest document ID
737539508
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/737539508
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