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Ethanol Induces Platelet Apoptosis
Author(s) -
Liu Lei,
Chen Mengxing,
Zhao Lili,
Zhao Qing,
Hu Renping,
Zhu Jie,
Yan Rong,
Dai Kesheng
Publication year - 2017
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13295
Subject(s) - platelet , apoptosis , in vivo , pathogenesis , hemostasis , chemistry , bleeding time , platelet activation , thrombin , pharmacology , medicine , immunology , biology , biochemistry , platelet aggregation , microbiology and biotechnology
Background 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. Methods Washed human platelets were pretreated with ethanol (EtOH), and apoptotic events and platelet function were detected. In in vivo experiments, C57 BL /6J mice were given EtOH by gavage. Platelet counts, tail bleeding time, and the stomach were examined. Results 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 NH 2‐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. Conclusions 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.