|
|
Blood, 15 January 2006, Vol. 107, No. 2, pp. 508-513.
Prepublished online as a Blood First Edition Paper on September 15, 2005; DOI 10.1182/blood-2005-07-2676.
Previous Article | Table of Contents | Next Article 
HEMATOPOIESIS
PKC controls protection against TRAIL in erythroid progenitors
Prisco Mirandola,
Giuliana Gobbi,
Cristina Ponti,
Ivonne Sponzilli,
Lucio Cocco, and
Marco Vitale
From the Department of Anatomy, Pharmacology, & Forensic Medicine, Human Anatomy Section, University of Parma, Ospedale Maggiore, Parma, Italy; the Department of Normal Human Morphology, University of Trieste, Italy; the Department of Anatomical Sciences, Cellular Signaling Laboratory, University of Bologna, Italy; and Istituto per i Trapianti d'Organo e ImmunocitologiaConsiglio Nazionale delle Ricerche (ITOI-CNR), Bologna Unit, Italy.
Apoptosis plays a central role in the regulation of the size of the hematopoietic stem cell pool as well as in the processes of cell differentiation along the various hematopoietic lineages. TRAIL is a member of the TNF family of cytokines with a known apoptogenic role against a variety of malignant cells and an emerging role in the modulation of normal hematopoiesis. Here we worked on the hypothesis that PKC could act as a switch of the cellular response to TRAIL during erythropoiesis. We demonstrate that EPO-induced erythroid CD34 cells are insensitive to the apoptogenic effect of TRAIL at day 0 due to the lack of specific receptor expression. From day 3 onward, erythroid cells express surface death receptors and become sensitive to TRAIL up to day 7/8 when, notwithstanding death-receptor expression, the EPO-driven up-regulation of PKC intracellular levels renders differentiating erythroid cells resistant to TRAIL likely via Bcl-2 up-regulation. Our conclusion is that in human CD34 cells, EPO promotes a series of events that, being finely regulated in their kinetics, restricts the sensitivity of these cells to TRAIL to a specific period of time, which therefore represents the "TRAIL window" for the negative regulation of erythroid-cell numbers.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
Related Article in Blood Online:
-
Closing the TRAIL to the DISC
- Robert T. Means, Jr
Blood 2006 107: 418-419.
[Full Text]
[PDF]
This article has been cited by other articles:

|
 |

|
 |
 
G. Gobbi, P. Mirandola, I. Sponzilli, C. Micheloni, C. Malinverno, L. Cocco, and M. Vitale
Timing and Expression Level of Protein Kinase C{varepsilon} Regulate the Megakaryocytic Differentiation of Human CD34 Cells
Stem Cells,
September 1, 2007;
25(9):
2322 - 2329.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Zamai, C. Ponti, P. Mirandola, G. Gobbi, S. Papa, L. Galeotti, L. Cocco, and M. Vitale
NK Cells and Cancer
J. Immunol.,
April 1, 2007;
178(7):
4011 - 4016.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|