Omi/HtrA2 and XIAP are components of platelet apoptosis signalling

Jeannine Winkler; Margaret L. Rand; Markus Schmugge; Oliver Speer

doi:10.1160/TH12-06-0404

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 109(03): 532-539
DOI: 10.1160/TH12-06-0404

Platelets and Blood Cells

Schattauer GmbH

Omi/HtrA2 and XIAP are components of platelet apoptosis signalling

Jeannine Winkler

¹Division of Haematology and Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland

²Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland, University of Zurich, Switzerland

,

Margaret L. Rand

³Division of Haematology / Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada

,

Markus Schmugge

¹Division of Haematology and Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland

,

Oliver Speer

¹Division of Haematology and Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland

²Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland, University of Zurich, Switzerland

› Author Affiliations

Abstract

Summary

Although platelets possess the hallmarks of apoptosis such as activation of caspases, cytochrome c release and depolarisation of the mitochondrial transmembrane potential (ΔΨm), their entire apoptotic-signalling pathway is not totally understood. Therefore we studied the expression of various apoptotic proteins and found that platelets contain the pro-apoptotic proteins Omi/HtrA2 and Smac/Diablo, as well as their target the X-linked inhibitor of apoptosis XIAP. Omi/HtrA2 and Smac/Diablo were released from mitochondria into the platelet cytosol together with cytochrome c after induction of apoptosis by the Ca²⁺ ionophore A23187 or the BH3 mimetic ABT-737, and to a lesser extent, after platelet stimulation with collagen and thrombin. Inhibition of Omi/HtrA2 led to decreased levels of activated caspase-3/7 and caspase-9, but did not abolish loss of ΔΨm or prevent release of Omi/HtrA2 from mitochondria. These results indicate that platelets have a functional intrinsic apoptotic-signalling pathway including the pro-apoptotic protease Omi/HtrA2 and its target protein XIAP.

Keywords

Apoptosis - caspase-3 - platelets - Omi/HtrA2 - XIAP

Full Text

References

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