title: Ethanol Induces Platelet Apoptosis.
abstract: Alcohol abuse incurs severe medical conditions, such as thrombocytopenia and hemorrhage, but the pathogenesis is not totally understood. Alcohol has been reported to induce apoptosis in eukaryotic cells, such as hepatocyte, nerve cell, corneal fibroblasts. However, it is still unclear whether alcohol induces platelet apoptosis.
  
  
  
  Washed human platelets were pretreated with ethanol (EtOH), and apoptotic events and platelet function were detected. In in vivo experiments, C57BL/6J mice were given EtOH by gavage. Platelet counts, tail bleeding time, and the stomach were examined.
  
  
  
  EtOH dose dependently induces depolarization of mitochondrial inner transmembrane potential, up-regulation of Bax, down-regulation of Bcl-2, and caspase-3 activation. EtOH does not induce surface expression of P-selectin or PAC-1 binding, whereas significantly reduces collagen-, thrombin-, and ADP-induced platelet aggregation. Moreover, EtOH induces c-Jun NH2-terminal kinase activation. In an in vivo mouse model of the acute alcoholism, EtOH significantly reduces the number of circulating platelets, prolongs the tail bleeding time, and causes gastric mucosa hemorrhage.
  
  
  
  These data demonstrate that EtOH induces mitochondria-mediated intrinsic platelet apoptosis, results in the reduction of the number of circulating platelets, and impairs in vivo hemostasis. These findings reveal the possible pathogenesis of hemorrhagic symptoms in patients experiencing acute alcohol intoxication.
authors.affiliation: Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
authors.forename: Mengxing
authors.initials: M
authors.lastname: Chen
authors.affiliation: Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
authors.forename: Renping
authors.initials: R
authors.lastname: Hu
authors.affiliation: Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yan
authors.affiliation: Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
authors.forename: Kesheng
authors.initials: K
authors.lastname: Dai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D006801:Humans; D066298:In Vitro Techniques; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010976:Platelet Count; D010979:Platelet Function Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: C494827:Bax protein, mouse; D002492:Central Nervous System Depressants; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000431:Ethanol; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Apoptosis; Ethanol; Platelet