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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

PLC gamma 2 and PKC Are Important to Myeloid Lineage Commitment Triggered by M-SCF and G-CSF

Texto completo
Autor(es):
Vaz Barbosa, Christiano Marcello [1] ; Bincoletto, Claudia [2] ; Barros, Carlos Castilho [3] ; Ferreira, Alice T. [1] ; Paredes-Gamero, Edgar J. [4, 1]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Dept Biofis, BR-04044020 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Dept Farmacol, BR-04044020 Sao Paulo - Brazil
[3] Univ Fed Pelotas, Dept Nutr, BR-96010610 Pelotas, RS - Brazil
[4] Univ Fed Sao Paulo, Dept Bioquim, BR-04044020 Sao Paulo - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: Journal of Cellular Biochemistry; v. 115, n. 1, p. 42-51, JAN 2014.
Citações Web of Science: 11
Resumo

Myeloid differentiation is a complex process whereby mature granulocytes or monocytes/macrophages are derived from a common myeloid progenitor through the coordinated action of hematopoietic cytokines. In this study, we explored the role of the Ca-i(2+) signaling transduction pathway in the commitment of hematopoietic stem/progenitor cells to either the monocytic or granulocytic lineage in response to macrophage colony-stimulating factor (M-CSF) and granulocyte colony-stimulating factor (G-CSF). M-CSF and G-CSF induce cell expansion and monocyte or granulocyte differentiation, respectively, without affecting the percentage of hematopoietic progenitor cells. Colony-forming units (CFUs) and flow cytometry demonstrated the involvement of phospholipase C (PLC) and protein kinase C (PKC) in monocyte/granulocyte commitment. In addition, using flow cytometry and RNA interference, we identified PLC2 as the PLC isoform that participates in this cell expansion and differentiation. Differences in signaling elicited by M-CSF and G-CSF were observed. The M-CSF-related effects were associated with the activation of ERK1/2 and nuclear factor of activated T-cells (NFAT); the inhibition of both molecules reduced the number of colonies in a CFU assay. In contrast, using flow cytometry and confocal evaluation, we demonstrated that G-CSF activated Jak-1 and STAT-3. Additionally, the effects induced by G-CSF were also related with the participation of Ca2+ calmodulin kinase II and the transcription factor PU.1. STAT-3 activation and the increase of PU.1 expression were sensitive to PLC inhibition by U73122. These data show that PLC2 and PKC are important upstream signals that regulate myelopoiesis through cytokines, and differences in M-CSF and G-CSF downstream signaling were identified. J. Cell. Biochem. 115: 42-51, 2014. (c) 2013 Wiley Periodicals, Inc. (AU)

Processo FAPESP: 07/58589-9 - Estudo da sinalização do Ca2+intracelular na auto-renovação, diferenciação e apoptose de células hematopoéticas
Beneficiário:Christiano Marcello Vaz Barbosa
Linha de fomento: Bolsas no Brasil - Doutorado