Anandamide extends platelets survival through CB(1)-dependent Akt signaling.
Platelets are stored at 22 degrees C, since incubation at 37 degrees C results in loss of viability. Nonetheless, in our body (37 degrees C), platelets survive for 8-10 days. This discrepancy has been explained in terms of deprivation of viability factors or accumulation of apoptotic factors during storage. We report that the endocannabinoid anandamide (AEA) may be one of the agents allowing platelet survival. In fact, at 37 degrees C, human platelets enhance the expression of pro-apoptotic proteins (caspases, Bax, Bak) and decrease the expression of Bcl-xL, thus changing the Bcl-xL/Bak ratio, a key platelet biological clock. AEA or its non-hydrolyzable analogue, methanandamide, extend platelet life span, without reversing the changes in Bcl-xL/Bak ratio induced by heat stress. Instead, AEA binding to type-1 cannabinoid receptor activates Akt, which regulates, through phosphorylation of Bad, the interactions among different Bcl-2 family members. These findings could have implications for platelet collection and, potentially, for their clinical use.
Catani
Maria Valeria
MV
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy.
Gasperi
Valeria
V
Evangelista
Daniela
D
Finazzi Agrò
Alessandro
A
Avigliano
Luciana
L
Maccarrone
Mauro
M
D000328:Adult; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001793:Blood Preservation; D002186:Cannabinoids / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D063388:Endocannabinoids; D006801:Humans; D053284:Polyunsaturated Alkamides / Q000378:metabolism / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013048:Specimen Handling
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; C088155:methanandamide; D051057:Proto-Oncogene Proteins c-akt; C078814:anandamide