levels of endogenous ceramide and protein kinase C-zeta (PKC-zeta) catalytic activity in HL-60 myeloid cells. ATRA induced a parallel increase of ceramide and catalytically active PKC-zeta into the nuclear compartment of HL-60 cells (peak at 72 h). On the other hand, vitamin D3 increased the levels of nuclear ceramide and PKC-zeta activity to a lesser extent and with a delayed kinetics compared to ATRA (peak at 96 h). Pretreatment of HL-60 cells with high pharmacological concentrations of exogenously-added C2-ceramide (10(-6) M) completely blocked the ATRA-mediated activation of nuclear PKC-zeta. Exogenous C2-ceramide (10(-6) M) also inhibited the granulocytic differentiation induced by ATRA, whereas it did not affect monocytic differentiation mediated by vitamin D3. Transient transfection experiments performed with a plasmid construct containing a constitutively active mutated form of the PKC-zeta cDNA fused in 3' to a fluorescent tag protein (pEGFP-PKC-zeta) demonstrated that the overexpression of catalytically active PKC-zeta was not accompanied by the appearance of a differentiated morphology. These findings suggest that nuclear PKC-zeta is necessary but not sufficient to induce granulocytic differentiation of HL-60 myeloid malignant cells.

Accumulation of catalytically active PKC-zeta into the nucleus of HL-60 cell line plays a key role in the induction of granulocytic differentiation mediated by all-trans retinoic acid

BERTOLASO, Lucia;SECCHIERO, Paola;PREVIATI, Maurizio;FALGIONE, Daniela;CAPITANI, Silvano;ZAULI, Giorgio
1998

Abstract

levels of endogenous ceramide and protein kinase C-zeta (PKC-zeta) catalytic activity in HL-60 myeloid cells. ATRA induced a parallel increase of ceramide and catalytically active PKC-zeta into the nuclear compartment of HL-60 cells (peak at 72 h). On the other hand, vitamin D3 increased the levels of nuclear ceramide and PKC-zeta activity to a lesser extent and with a delayed kinetics compared to ATRA (peak at 96 h). Pretreatment of HL-60 cells with high pharmacological concentrations of exogenously-added C2-ceramide (10(-6) M) completely blocked the ATRA-mediated activation of nuclear PKC-zeta. Exogenous C2-ceramide (10(-6) M) also inhibited the granulocytic differentiation induced by ATRA, whereas it did not affect monocytic differentiation mediated by vitamin D3. Transient transfection experiments performed with a plasmid construct containing a constitutively active mutated form of the PKC-zeta cDNA fused in 3' to a fluorescent tag protein (pEGFP-PKC-zeta) demonstrated that the overexpression of catalytically active PKC-zeta was not accompanied by the appearance of a differentiated morphology. These findings suggest that nuclear PKC-zeta is necessary but not sufficient to induce granulocytic differentiation of HL-60 myeloid malignant cells.
1998
Bertolaso, Lucia; Gibellini, D; Secchiero, Paola; Previati, Maurizio; Falgione, Daniela; Visani, G; Rizzoli, R; Capitani, Silvano; Zauli, Giorgio...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/517093
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