ABSTRACT
Livin is a member of the inhibitor of apoptosis proteins (IAP) family of intracellular antiapoptotic proteins that act by binding and inhibiting caspases. Upon strong apoptotic stimuli, it is then specifically cleaved by caspases to produce a truncated protein (tLivin) with a paradoxical proapoptotic activity. Intriguingly, we have detected robust protein levels of Livin in normal mature bone marrow megakaryocyte (MK) and platelets. To evaluate the potential role of Livin in thrombopoiesis, we used the human BCR-ABL+ cell line, LAMA-84, and cord blood CD34+ cells to induce differentiation toward MKs. Upon differentiation, induced by phorbol myristate acetate and concurrent with increase in Livin protein expression, LAMA-84 cells formed functional platelet-like particles. Livin overexpression in CD34+ progenitor cells induced higher endoreplication in the MKs generated. Furthermore, overexpression of Livin increased the ability of both primary MKs and differentiated LAMA-84 cells to produce functional platelets. In the differentiated LAMA-84 cells, we observed accumulation of proapoptotic tLivin concomitant with increased caspase-3 activity. Downregulation of Livin with small interfering RNA in both leukemic and primary MK cells decreased their ability to produce functional platelets. We suggest that Livin has a role in thrombopoiesis by regulating the apoptotic and antiapoptotic balance in MK endoreplication and platelet production.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Blood Platelets/cytology , Blood Platelets/metabolism , Inhibitor of Apoptosis Proteins/metabolism , Megakaryocytes/cytology , Neoplasm Proteins/metabolism , Adaptor Proteins, Signal Transducing/genetics , Antigens, CD34/metabolism , Apoptosis/genetics , Apoptosis/physiology , Cell Differentiation/genetics , Cell Differentiation/physiology , Cell Line, Tumor , Humans , Inhibitor of Apoptosis Proteins/genetics , Neoplasm Proteins/genetics , RNA, Small Interfering/geneticsABSTRACT
Assessment of the umbilical cord gases at birth is an objective measurement of the neonatal condition. However, previous studies have shown that the results are unreliable in one out of four paired samples. The aim of our study was to assess the sampling of cord gases after operative deliveries. We found out that the error rate in our unit was 39% and the erroneous sampling was more common in arterial samples and in deliveries that happened during the night. We believe that assessment of the results obtained from paracentesis of the umbilical vessels helps to evaluate the quality of the sampling and to identify preventable causes of error.
