JNK and p38 are activated by erythropoietin (EPO) but are not induced in apoptosis following EPO withdrawal in EPO-dependent HCD57 cells
JNK and p38 are activated by erythropoietin (EPO) but are not induced in apoptosis following EPO withdrawal in EPO-dependent HCD57 cells
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DOI：
10.1182/blood.v96.3.933.015k52_933_940
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发表时间：
2000-08-01
期刊：
影响因子：
20.3
通讯作者：
Sawyer, ST
中科院分区：
文献类型：
--
作者：
Jacobs-Helber, SM;Ryan, JJ;Sawyer, ST
Jun N 末端激酶 (JNK) 和 p38 是丝氨酸/苏氨酸激酶丝裂原激活蛋白激酶家族的成员，由于细胞应激而被激活，但也可能在生长因子诱导的许多细胞的增殖和/或存活或分化中发挥作用。最近的一份报告表明 JNK 和 p38 在 EPO 撤除后诱导促红细胞生成素 (EPO) 依赖性红系细胞系 HCD57 凋亡中起作用，而我们之前报道的数据并不支持 JNK 在生长因子撤除诱导的 HCD57 细胞凋亡中的作用。因此，进一步检测JNK是否在EPO撤除诱导的细胞凋亡中被激活；该研究扩展到 p38，并表征了 EPO 对 JNK 和 p38 活性的影响。用 EPO 处理 HCD57 细胞导致 JNK 和 p38 活性逐渐且持续的激活；这些活性在 EPO 撤除后降低，还检测到 p42/p44 细胞外信号相关激酶 (ERK) 的瞬时激活。抑制 ERK 活性可抑制 EPO 处理细胞的增殖，但既不诱导凋亡，也不激活 JNK。抑制 p38 活性可抑制增殖，但不能保护 HCD57 细胞免受 EPO 撤除诱导的凋亡。用肿瘤坏死因子-α 处理 HCD57 细胞可诱导 JNK 激活，但不诱导细胞凋亡。这些结果表明 JNK、p38 和 ERK 在 EPO 诱导的红系细胞增殖和/或存活中发挥作用，但不支持 JNK 或 p38 在 EPO 从红系细胞中撤出诱导的细胞凋亡中发挥作用（美国血液学会 (C) 2000）。
Jun N-terminal kinase (JNK) and p38, members of the mitogen-activated protein kinase family of serine/threonine kinases, are activated as a result of cellular stress but may also play a role in growth factor-induced proliferation and/or survival or differentiation of many cells. A recent report has implicated JNK and p38 in the induction of apoptosis in the erythropoietin (EPO)-dependent erythroid cell line HCD57 following EPO withdrawal, whereas our previously reported data did not support a role for JNK in growth factor withdrawal-induced apoptosis in HCD57 cells. Therefore, further testing was done to see if JNK was activated in EPO withdrawal-induced apoptosis; the study was extended to p38 and characterized the effect of EPO on JNK and p38 activities, Treatment of HCD57 cells with EPO resulted in a gradual and sustained activation of both JNK and p38 activity; these activities decreased on EPO withdrawal, Transient activation of p42/p44 extracellular signal-related kinases (ERK) was also detected. Inhibition of ERK activity inhibited proliferation in EPO-treated cells but neither induced apoptosis nor activated JNK, Inhibition of p38 activity inhibited proliferation but did not protect HCD57 cells from apoptosis induced by EPO withdrawal, Treatment of HCD57 cells with tumor necrosis factor-alpha induced JNK activation but did not induce apoptosis. These results implicate JNK, p38, and ERK in EPO-induced proliferation and/or survival of erythroid cells but do not support a role for JNK or p38 in apoptosis induced by EPO withdrawal from erythroid cells, (C) 2000 by The American Society of Hematology.