Platelet apoptosis by cold‐induced glycoprotein Ibα clustering
Background: Cold‐storage of platelets followed by rewarming induces changes in Glycoprotein (GP) Ibα‐distribution indicative of receptor clustering and initiates thromboxane A2‐formation. GPIbα is associated with 14‐3‐3 proteins, which contribute to GPIbα‐signaling and in nucleated cells take part...
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Published in | Journal of thrombosis and haemostasis Vol. 8; no. 11; pp. 2554 - 2562 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
01.11.2010
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Subjects | |
Online Access | Get full text |
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Summary: | Background: Cold‐storage of platelets followed by rewarming induces changes in Glycoprotein (GP) Ibα‐distribution indicative of receptor clustering and initiates thromboxane A2‐formation. GPIbα is associated with 14‐3‐3 proteins, which contribute to GPIbα‐signaling and in nucleated cells take part in apoptosis regulation.
Objectives and methods: We investigated whether GPIbα‐clustering induces platelet apoptosis through 14‐3‐3 proteins during cold (4 h 0 °C)‐rewarming (1 h 37 °C).
Results: During cold‐rewarming, 14‐3‐3 proteins associate with GPIbα and dissociate from Bad inducing Bad‐dephosphorylation and activation. This initiates pro‐apoptosis changes in Bax/Bcl‐xL and Bax‐translocation to the mitochondria, inducing cytochrome c release. The result is activation of caspase‐9, which triggers phosphatidylserine exposure and platelet phagocytosis by macrophages. Responses are prevented by N‐acetyl‐d‐glucosamine (GN), which blocks GPIbα‐clustering, and by O‐sialoglycoprotein endopeptidase, which removes extracellular GPIbα.
Conclusions: Cold‐rewarming triggers apoptosis through a GN‐sensitive GPIbα‐change indicative of receptor clustering. Attempts to improve platelet transfusion by cold‐storage should focus on prevention of the GPIbα‐change. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1538-7933 1538-7836 1538-7836 |
DOI: | 10.1111/j.1538-7836.2010.04043.x |