Omi/HtrA2 and XIAP are components of platelet apoptosis signalling

Thromb Haemost. 2013 Mar;109(3):532-9. doi: 10.1160/TH12-06-0404. Epub 2013 Jan 10.

Abstract

Although platelets possess the hallmarks of apoptosis such as activation of caspases, cytochrome c release and depolarisation of the mitochondrial transmembrane potential (∆Ψm), 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 ∆Ψm 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Biphenyl Compounds / pharmacology
  • Blood Platelets / metabolism*
  • Blood Platelets / pathology*
  • Calcimycin / pharmacology
  • Calcium / metabolism
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Collagen / metabolism
  • Cytochromes c / metabolism
  • Cytoplasm / metabolism
  • Dose-Response Relationship, Drug
  • Flow Cytometry / methods
  • High-Temperature Requirement A Serine Peptidase 2
  • Humans
  • Ionophores / metabolism
  • Membrane Potential, Mitochondrial
  • Mitochondrial Proteins / metabolism*
  • Nitrophenols / pharmacology
  • Piperazines / pharmacology
  • Serine Endopeptidases / metabolism*
  • Signal Transduction*
  • Sulfonamides / pharmacology
  • Thrombin / metabolism
  • X-Linked Inhibitor of Apoptosis Protein / metabolism*

Substances

  • ABT-737
  • Biphenyl Compounds
  • Ionophores
  • Mitochondrial Proteins
  • Nitrophenols
  • Piperazines
  • Sulfonamides
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • Calcimycin
  • Collagen
  • Cytochromes c
  • Serine Endopeptidases
  • HTRA2 protein, human
  • High-Temperature Requirement A Serine Peptidase 2
  • Thrombin
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9
  • Calcium