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Activation of Rafl and the ERK pathway in response to L-ascorbic acid in acute myeloid leukemia cells

机译:急性髓系白血病细胞中Raf和ERK途径对L-抗坏血酸的反应

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摘要

L-ascorbic acid (LAA) shows cytotoxicity and induces apoptosis of malignant cells in vitro, but the mechanisms by which such effects occur have not been elucidated. In the present study, we provide evidence that the ERK MAP kinase pathway is activated in response to LAA (< 1 mM) in acute myeloid leukemia cell lines. LAA treatment of cells induces a dose-dependent phosphorylation of extracellular signal-regulated kinases (ERK) and results in activation of its catalytic domain. Our data also demonstrate that the small G protein Raf1 and MAPKactivated protein kinase 2 are activated by LAA as an upstream and a downstream regulator of ERK, respectively. Although the ERK pathway has been known to activate cell proliferation, pharmacologic inhibition of ERK reduces LAA-dependent apoptosis and growth inhibitory response of acute myeloid leukemia cell lines, suggesting that this signaling cascade positively regulates induction of apoptotic response by LAA. (C) 2004 Elsevier Inc. All rights reserved.
机译:L-抗坏血酸(LAA)在体外显示出细胞毒性并诱导恶性细胞凋亡,但尚未阐明这种作用发生的机制。在本研究中,我们提供证据表明,ERK MAP激酶途径在急性髓样白血病细胞系中响应LAA(<1 mM)而被激活。细胞的LAA处理会诱导细胞外信号调节激酶(ERK)的剂量依赖性磷酸化,并导致其催化结构域的活化。我们的数据还表明,小G蛋白Raf1和MAPK激活的蛋白激酶2被LAA分别激活为ERK的上游和下游调节剂。尽管已知ERK途径可激活细胞增殖,但ERK的药理抑制作用可降低急性髓样白血病细胞系的LAA依赖性凋亡和生长抑制反应,这表明该信号级联反应正调控LAA对细胞凋亡反应的诱导。 (C)2004 Elsevier Inc.保留所有权利。

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