Regulation of platelet lifespan by apoptosis.
The lifespan of platelets in circulation is brief, close to 10 days in humans and 5 days in mice. Bone marrow residing megakaryocytes produce around 100 billion platelets per day. In a healthy individual, the majority of platelets are not consumed by hemostatic processes, but rather their lifespan is controlled by programmed cell death, a canonical intrinsic apoptosis program. In the last decade, insights from genetically manipulated mouse models and pharmacological developments have helped to define the components of the intrinsic, or mitochondrial, apoptosis pathway that controls platelet lifespan. This review focuses on the molecular regulation of apoptosis in platelet survival, reviews thrombocytopenic conditions linked to enhanced platelet death, examines implications of chemotherapy-induced thrombocytopenia through apoptosis-inducing drugs in cancer therapy as well as discusses ex vivo aging of platelets.
a The Walter and Eliza Hall Institute of Medical Research , Melbourne , Australia.
Marion
M
Lebois
a The Walter and Eliza Hall Institute of Medical Research , Melbourne , Australia.|b Department of Medical Biology , The University of Melbourne , Melbourne , Australia.
Emma C
EC
Josefsson
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D001793:Blood Preservation; D020169:Caspases / Q000378:metabolism; D005786:Gene Expression Regulation; D006487:Hemostasis; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010718:Phosphatidylserines / Q000378:metabolism / Q000494:pharmacology; D017713:Platelet Transfusion; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013921:Thrombocytopenia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism
D000970:Antineoplastic Agents; D010718:Phosphatidylserines; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases