TNF-related apoptosis-inducing ligand (TRAIL) and erythropoiesis: a role for PKC epsilon |
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Authors: | Vitale M Gobbi G Mirandola P Ponti C Sponzilli I Rinaldi L Manzoli F A |
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Affiliation: | Department of Anatomy, Pharmacology & Forensic Medicine, University of Parma, Ospedale Maggiore, Via Gramsci, 14, I-43100 Parma, Italy. marco.vitale@unipr.it |
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Abstract: | The regulation of the hematopoietic stem cell pool size and the processes of cell differentiation along the hematopoietic lineages involve apoptosis. Among the different factors with a recognized activity on blood progenitor cells, TRAIL - a member of the TNF family of cytokines - has an emerging role in the modulation of normal hematopoiesis.PKC(epsilon) levels are regulated by EPO in differentiating erythroid progenitors and control the protection against the apoptogenic effect of TRAIL. EPO-induced erythroid CD34 cells are insensitive to the apoptogenic effect of TRAIL between day 0 and day 3, due to the lack of specific surface receptors expression. Death receptors appear after day 3 of differentiation and consequently erythroid cells become sensitive to TRAIL up to day 9/10, when the EPO-driven up-regulation of PKC epsilon intracellular levels inhibits the TRAIL-mediated apoptosis, via Bcl-2. In the time interval between day 3 and 9, therefore, the number of erythroid progenitors can be limited by the presence of soluble or membrane-bound TRAIL present in the bone marrow microenvironment. |
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