The inhibition of ERK/MAPK not the activation of JNK/SAPK is primarily required to induce apoptosis in chronic myelogenous leukemic K562 cells

다국어 초록 (Multilingual Abstract)

In this study, the downstream signaling of Ber-Abl tyrosine kinase responsible for apoptosis resistance was investigated DNA fragmentation, a hallmark of apoptosis, was observed after 2 days of herbimycin A treatment with a peak on 3 day. During the apoptosis induced by the treatment of herbimycin A, stress-activated protein kinase (SAPK) and p38 kinase were activated time-and dose-dependently, while extracellular signal-regulated kinase (ERK) was inhibited. However, apoptosis was induced by the treament of PD98059, a specific inhibitor of MEK(MAPK or ERK dinase), not by the treatment of sorbitol, a strong activator of SAPK and p38 kinase. Although K562 cells were very resistant to sorbitol-induced apoptosis. DNA fragmentation was induced rapidly in Jurkat, HL-60 and U937 cells after exposure to sorbitol, despite that these apoptosis-sensitive cells have similar or lower activities of JNK SAPK and p38 kinase compared with k562 cells after treatment of sorbitol. K562 cells had a much higher basal activity of ERK MAPK than other apoptosis-sensitive cell lines, which were very susceptible to apoptosis induced by low dose of PHD98059 compared with K562 cells. In HL-60 cells, sorbitol-induced apoptosis was prevented by the treatment of phorbol myristate 13-acetate (PMA), which activates the ERK MAPK pathway, and this was blocked by PD98059. From these results it could be suggested that the inhibition of ERK MAPK not the activation of JNK SAPK is primarily required to induce apoptosis in K562 cells. ⓒ 2000 Published by Elsevier Science Ltd. All rights reserved.