Expression of p21WAF1 Is Dependent on the Activation of ERK during Vitamin E-Succinate-induced Monocytic Differentiation

다국어 초록 (Multilingual Abstract)

Vitamin E-succinate (VES) induced monocytic differentiation
of HL-60 human leukemia cells. Treatment
with VES increased the nitroblue tetrazolium reduction
activity, and the expression of monocyte specific
cell surface antigen, CD14 and c-fms. During the
monocytic differentiation of HL-60 cells that were induced
by VES, the phosphorylation of extracellular
signal-regulated protein kinase (ERK) was increased
by 12 h and then gradually decreased to a level that
was similar to that of the control. However, the phosphorylation
levels of p38 and JNK, as well as the expression
levels of ERK, p38, and JNK, were unchanged
by the VES treatment. Treatment with VES
also induced hypophosphorylation of the retinoblastoma
protein and an increase of the p21WAF1 protein
level. VES-induced ERK phosphorylation was abolished
by the ERK inhibitor, PD98059, which resulted
in a remarkable prevention of VES-induced monocytic
differentiation. Inhibition of the ERK activity by
PD98059 also diminished the VES-induced p21WAF1
protein expression, but did not change the phosphorylation
state of the retinoblastoma protein. Collectively,
these data suggest that the ERK signaling pathway
mediates the up-regulation of the p21WAF1 expression
that is induced by VES, which is required for monocytic
differentiation of HL 60 cells.