Requirement for ERK activity in sodium selenite-induced apoptosis of acute promyelocytic leukemia-derived NB4 cells.
Our previous study has shown that sodium selenite can cause apoptosis in acute promyelocytic leukemia-derived NB4 cells in a caspase-dependent manner, but the detailed mechanism is unknown. Here we demonstrate a requirement for extracellular signal-regulated protein kinase (ERK) in mediating sodium selenite -induced apoptosis in NB4 cell. Though no apparent elevation of ERK activity was observed during the apoptosis in NB4 cells caused by 20 microM sodium selenite treatment, PD98059 and U0126, specific chemical inhibitors of the MEK/ERK signaling pathway, were shown to strongly prevent the apoptosis process, while ERK activator TPA enhanced the process. It is also known that p38 MAPK inhibitor SB203580 and JNK inhibitor SP600125 had slight effects on apoptosis. Further study indicated that ERK exerted its proapoptotic effect only at the early stage of apoptosis and played an antiapoptotic role at the later stages. Taken together, our findings suggest that ERK plays an active role in mediating sodium seleniteinduced apoptosis in NB4 cells.
Han
Bingshe
B
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Wei
Wei
W
Hua
Fangyuan
F
Cao
Tingming
T
Dong
Hua
H
Yang
Tao
T
Yang
Yang
Y
Pan
Huazhen
H
Xu
Caimin
C
D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology* / Q000473:pathology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018038:Sodium Selenite / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D047428:Protein Kinase Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D018038:Sodium Selenite; D013755:Tetradecanoylphorbol Acetate