In chronic myeloid leukemia K562 cells, differentiation is also blocked because of low levels of ganglioside GM3, derived by the high expression of sialidase Neu3 active on GM3. In this article, we studied the effects of Neu3 silencing (40-70% and 63-93% decrease in protein content and activity, respectively) in these cells. The effects were as follows: (a) gangliosides GM3, GM1, and sialosylnorhexaosylceramide increased markedly; (b) cell growth and [(3)H]thymidine incorporation diminished relevantly; (c) as mRNA, cyclin D2, and Myc were much less expressed, whereas cyclin D1 was expressed more like its inhibitor p21; (d) as mRNA, pro-apoptotic proteins Bax and Bad increased with concurrent decrease and increase in the anti-apoptotic proteins Bcl-2 and Bcl-XL, respectively; (e) the apoptosis inducers etoposide and staurosporine were active on Neu3 silencing cells but not on mock cells; (f) as mRNA, the megakaryocytic markers CD10, CD44, CD41, and CD61 increased similar to the case of mock cells stimulated with PMA; (g) the signaling cascades mediated by PLC-beta2, PKC, RAF, ERK1/2, RSK90, and JNK were largely activated. The induction of a GM3-rich ganglioside pattern in K562 cells by treatment with brefeldin A elicited a phenotype similar to that of Neu3 silencing cells. In conclusion, upon Neu3 silencing, K562 cells show a decrease in proliferation, propensity to undergo apoptosis, and megakaryocytic differentiation.
Silencing of membrane-associated sialidase Neu3 diminishes apoptosis resistance and triggers megakaryocytic differentiation of chronic myeloid leukemic cells K652 through the increase of ganglioside GM3 / C. Tringali, B. Lupo, F. Cirillo, N. Papini, L. Anastasia, G. Lamorte, P. Colombi, R. Bresciani, E. Monti, G. Tettamanti, B. Venerando. - In: CELL DEATH AND DIFFERENTIATION. - ISSN 1350-9047. - 16:1(2009 Jan), pp. 164-174.
|Titolo:||Silencing of membrane-associated sialidase Neu3 diminishes apoptosis resistance and triggers megakaryocytic differentiation of chronic myeloid leukemic cells K652 through the increase of ganglioside GM3|
TRINGALI, CRISTINA ALESSANDRA (Primo)
LUPO, BARBARA (Secondo)
TETTAMANTI, GUIDO (Penultimo)
VENERANDO, BRUNO (Ultimo)
|Parole Chiave:||sialidase ; Neu3 ; leukemia ; ganglioside ; K562 cells|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
|Data di pubblicazione:||gen-2009|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/cdd.2008.141|
|Appare nelle tipologie:||01 - Articolo su periodico|