1-beta-D-Arabinofuranosylcytosine stimulates ceramide and diglyceride formation in HL-60 cells.
The effect of 1-beta-D-arabinofuranosylcytosine (ara-C) on phospholipid metabolism was investigated in HL-60 cells. Treatment of cells with ara-C resulted in a time- and dose-dependent increase in the mass of ceramide and diglyceride. When cells were treated with 10 microM ara-C, an increase in the mass of ceramide and diglyceride was detectable at 5 min and reached a plateau at 30 min with a 2-fold increase compared to control cells. Treatment of cells with 10 microM ara-C resulted in the activation of neutral sphingomyelinase with a peak at 30 min that represented a 2-fold increase in specific activity. ara-C also increased expression of the transcription factor NF-kappa B which is related to the control of monocyte differentiation. These findings suggest that ara-C activates phospholipid hydrolytic pathways to generate second messengers that control gene expression and differentiation in the HL-60 cell line.
Strum
J C
JC
Department of Biochemistry, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1016.
Small
G W
GW
Pauig
S B
SB
Daniel
L W
LW
D002454:Cell Differentiation; D002460:Cell Line; D002518:Ceramides / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D003561:Cytarabine / Q000494:pharmacology*; D004075:Diglycerides / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D016328:NF-kappa B / Q000096:biosynthesis*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002518:Ceramides; D004075:Diglycerides; D016328:NF-kappa B; D003561:Cytarabine; D013108:Sphingomyelin Phosphodiesterase