title: Crucial role for endoplasmic reticulum stress during megakaryocyte maturation.
abstract: OBJECTIVE
  Apoptotic-like phase is an essential step for the platelet formation from megakaryocytes. How controlled is this signaling pathway remained poorly understood. The aim of this study was to determine whether endoplasmic reticulum (ER) stress-induced apoptosis occurs during thrombopoiesis.
  
  
  RESULTS
  Investigation of ER stress and maturation markers in different models of human thrombopoiesis (CHRF, DAMI, MEG-01 cell lines, and hematopoietic stem cells: CD34(+)) as well as in immature pathological platelets clearly indicated that ER stress occurs transiently during thrombopoiesis. Direct ER stress induction by tunicamycin, an inhibitor of N-glycosylation, or by sarco/endoplasmic reticulum Ca(2+) ATPase type 3b overexpression, which interferes with reticular calcium, leads to some degree of maturation in megakaryocytic cell lines. On the contrary, exposure to salubrinal, a phosphatase inhibitor that prevents eukaryotic translation initiation factor 2α-P dephosphorylation and inhibits ER stress-induced apoptosis, decreased both expression of maturation markers in MEG-01 and CD34(+) cells as well as numbers of mature megakaryocytes and proplatelet formation in cultured CD34(+) cells.
  
  
  CONCLUSIONS
  Taken as a whole, our research suggests that transient ER stress activation triggers the apoptotic-like phase of the thrombopoiesis process.
authors.affiliation: From the Inserm U770, Université Paris-Sud, Le Kremlin-Bicêtre, France (J.J.L., C.C., L.A., E.P., S.D., J.E., R.B.); INSERM UMR1009, Institut Gustave Roussy, Université Paris-Sud, Villejuif, France (A.P., K.L., N.D.); and Centre de Référence des Pathologies Plaquettaires, Plateforme Technologique d'Innovation Biomédicale, Hôpital Xavier Arnozan, Pessac, France (P.N.).
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Lopez
authors.forename: Alberta
authors.initials: A
authors.lastname: Palazzo
authors.forename: Chiraz
authors.initials: C
authors.lastname: Chaabane
authors.forename: Letizia
authors.initials: L
authors.lastname: Albarran
authors.forename: Evelyne
authors.initials: E
authors.lastname: Polidano
authors.forename: Kristell
authors.initials: K
authors.lastname: Lebozec
authors.forename: Saoussen
authors.initials: S
authors.lastname: Dally
authors.forename: Paquita
authors.initials: P
authors.lastname: Nurden
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Enouf
authors.forename: Najet
authors.initials: N
authors.lastname: Debili
authors.forename: Régis
authors.initials: R
authors.lastname: Bobe
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008533:Megakaryocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D034061:Thrombopoiesis / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D015852:Eukaryotic Initiation Factor-2; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506949:ATP2A3 protein, human
keywords: apoptosis; endoplasmic reticulum stress; platelet; thrombopoiesis