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首页> 外文期刊>Cellular Physiology and Biochemistry >4-aminopyridine Induces Apoptosis of Human Acute Myeloid Leukemia Cells via Increasing [Ca2+]i Through P2X7 Receptor Pathway
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4-aminopyridine Induces Apoptosis of Human Acute Myeloid Leukemia Cells via Increasing [Ca2+]i Through P2X7 Receptor Pathway

机译:4-氨基吡啶通过通过P2X7受体途径增加[Ca2 +] i诱导人急性髓性白血病细胞凋亡。

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4-AP, a voltage-gated potassium channel blocker, was identified to exert critical pro-apoptotic properties in various types of cancer cells. The present study aims to explore the effect of 4-AP on the apoptosis of human AML cells and the underlying mechanism. We found 4-AP inhibited the proliferation and induces apoptosis in both AML cell lines and primary cultured human AML cells. The apoptosis of AML cells after 4-AP treatment was further confirmed by the disruption of mitochondrial membrane potential (MMP) and activation of caspase 3 and 9. 4-AP inhibited Kv currents in NBsub4/sub, HL-60 and THP-1 cells. Furthermore, 4-AP induced significant increment in [Casup2+/sup]subi/sub, which were inhibited by KN-62, a specific blocker of Psub2/subXsub7/sub receptors. KN-62 also abrogated 4-AP induced apoptosis. Knockdown of Psub2/subXsub7/sub receptor by small interfering RNA blocked the effect of 4-AP. Conclusively, this study indicated that 4-AP promotes apoptosis in human AML cells via increasing [Casup2+/sup]subi/sub through Psub2/subXsub7/sub receptor.
机译:电压门控钾通道阻滞剂4-AP被鉴定为在各种类型的癌细胞中发挥关键的促凋亡特性。本研究旨在探讨4-AP对人AML细胞凋亡的影响及其潜在机制。我们发现4-AP在AML细胞系和原代培养的人AML细胞中均抑制增殖并诱导凋亡。线粒体膜电位(MMP)的破坏以及caspase 3和9的活化进一步证实了4-AP处理后AML细胞的凋亡。4-AP抑制了NB 4 ,HL-中的Kv电流。 60和THP-1细胞。此外,4-AP诱导了[Ca 2 + ] i 的显着增加,这被P 2 X 7 受体。 KN-62也废除了4-AP诱导的细胞凋亡。 P 2 X 7 受体通过小干扰RNA敲低阻断了4-AP的作用。结论是,这项研究表明4-AP通过增加P 2 X [Ca 2 + ] i 促进人AML细胞凋亡> 7 受体。

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