pituitrin and Thrombocytopenia

Platelet shedding from mature megakaryocytes (MKs) in thrombopoiesis is the critical step for elevating circulating platelets fast and efficiently, however, the underlying mechanism is still not well-illustrated, and the therapeutic targets and candidates are even less.. In order to investigate the mechanisms for platelet shedding after vasopressin treatment and find new therapeutic targets for thrombocytopenia.. Platelet production was evaluated both in vivo and in vitro after arginine vasopressin (AVP) administration. The underlying biological mechanism of AVP-triggered thrombopoiesis were then investigated by a series of molecular and bioinformatics techniques.. it is observed that proplatelet formation and platelet shedding in the final stages of thrombopoiesis promoted by AVP, an endogenous hormone, can quickly increases peripheral platelets. This rapid elevation is thus able to speed up platelet recovery after radiation as expected. The mechanism analysis reveal that proplatelet formation and platelet release from mature MKs facilitated by AVP is mainly mediated by Akt-regulated mitochondrial metabolism. In particular, phosphorylated Akt regulates mitochondrial metabolism through driving the association of hexokinase-2 with mitochondrial voltage dependent anion channel-1 in AVP-mediated thrombopoiesis. Further studies suggest that this interaction is stabilized by IκBα, the expression of which is controlled by insulin-regulated membrane aminopeptidase.. these data demonstrate that phosphorylated Akt-mediated mitochondrial metabolism regulates platelet shedding from MKs in response to AVP, which will provide new therapeutic targets and further drug discovery clues for thrombocytopenia treatment.

Topics: Blood Platelets; Humans; Megakaryocytes; Proto-Oncogene Proteins c-akt; Thrombocytopenia; Thrombopoiesis; Vasopressins

Topics: Gastrointestinal Hemorrhage; Humans; Infusions, Intra-Arterial; Thrombocytopenia; Vasopressins

Topics: Acute Kidney Injury; Antibody Formation; Blood Coagulation; Blood Pressure; Calcium; Catecholamines; Complement Activation; Extracorporeal Circulation; Hemodynamics; Hemolysis; Humans; Immunity, Cellular; Intracranial Embolism and Thrombosis; Leukocytes; Potassium; Pulmonary Circulation; Thrombocytopenia; Vasopressins

The literature suggests that platelets might help mediate the pulmonary vascular pressor response to hypoxia. This study evaluated the hypoxic response in thrombocytopenic dogs. Platet depletion was achieved in five dogs by the use of platelet antiserum. In the normoxic state these dogs had lower cardiac outputs and higher pulmonary and systemic vascular resistances than five control dogs. The pressor response to hypoxia in these dogs was not only preserved but considerably enhanced in comparison to the control dogs. Hypoxia increased the pulmonary vascular resistance 146 +/- 17% above its normoxic value in the thrombocytopenic dogs and 64 +/- 21% in the control dogs. Thus platelets may normally produce a dilator substance or inactivate a pressor substance during hypoxia. The mechanism of the effect is not apparent but it is clear tha the pulmonary pressor response to hypoxia in the dog is not mediated by platelets.

Topics: Animals; Blood Cell Count; Blood Platelets; Blood Pressure; Cardiac Output; Dogs; Hypoxia; Lung; Prostaglandins F; Thrombocytopenia; Vascular Resistance; Vasopressins