Thymosin β4 and AcSDKP inhibit the proliferation of HL-60 cells and induce their differentiation and apoptosis
Thymosin β4 and AcSDKP inhibit the proliferation of HL-60 cells and induce their differentiation and apoptosis
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DOI：
10.1016/j.cellbi.2006.01.009
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发表时间：
2006-06-01
影响因子：
3.9
通讯作者：
Wang, Qi Ru
中科院分区：
文献类型：
--
作者：
Huang, Wei Qi;Wang, Bao He;Wang, Qi Ru
我们以前的工作表明，骨髓基质细胞分泌胸腺素β 4（T β 4）和AcSDKP。骨髓内皮细胞条件培养液中存在T β 4和AcSDKP。胸腺素P4由43个多肽组成，分子量为4963。其N-末端含有乙酰化四肽Ac-N-Ser-Asp-Lys-Pro（AcSDKP）序列。本研究旨在探讨T4和AcSDKP对HL-60细胞生长的影响。结果表明，T β 4（10（-11）-10（-7）mol/L）和AcSDKP（10（-11）-10（-7）mol/L）对HL-60细胞的增殖具有剂量依赖性抑制作用。从细胞形态学和NBT还原的角度观察T4和AcSDKP对HL-60细胞的诱导分化作用.形态学和DNA片段分析证明T β 4和AcSDKP可诱导HL-60细胞凋亡。为探讨T β 4和AcSDKP对HL-60白血病细胞内游离钙离子浓度（[Ca 2 +]（i））的影响机制，采用Atlas cDNA表达芯片技术检测了细胞内游离钙离子浓度（[Ca 2 +]（i））。结果表明，T β 4和AcSDKP可通过刺激细胞内Ca ~（2+）库释放Ca ~（2+），增加[Ca ~（2+）]（i）。此外，AcSDKP还能诱导HL-60细胞外钙内流。T4还能改变白血病细胞凋亡相关基因的表达，抑制白血病细胞的增殖，诱导白血病细胞分化和凋亡。(c)2006年国际细胞生物学联合会。由爱思唯尔有限公司出版。保留所有权利。
Our previous works have shown that bone marrow stromal cells secrete thymosin beta 4 (T beta 4) and AcSDKP. T beta 4 and AcSDKP are existed in the conditioned medium of bone marrow endothelial cells. They exerted inhibitory effects on hematopoietic cells and then had protective effect on the early hematopoietic cells, which were cultured in the presence of hernatopoietic stimulators.Thymosin P4 consists of 43 peptides with a molecular weight of 4963. It contains at its N-terminal end the sequence of the acetylated tetrapeptide Ac-N-Ser-Asp-Lys-Pro (AcSDKP). This study was performed to evaluate the effect of T 4 and AcSDKP on the growth of HL-60 cells. It was showed that T beta 4 (10(-11)-10(-7) mol/L) and AcSDKP (10(-11)-10(-7) mol/L) had the dose-dependent inhibitory effect on the proliferation of HL-60 cells. Based on cell morphology and NBT reduction, T 4 and AcSDKP induced differentiation of HL-60 cells. Morphologic and DNA fragment analysis proved that T beta 4 and AcSDKP induced apoptosis of HL-60 cells. In order to analyze the mechanism of the effects of T beta 4 and AcSDKP, intracellular free Ca2+ concentration ([Ca2+](i)) of HL-60 leukemic cells was tested and Atlas cDNA Expression Array was performed. The results showed that T beta 4 and AcSDKP could increased [Ca2+](i) by stimulating the release of Ca2+ from intracellular Ca2+ pool. Moreover, AcSDKP could also elicit a potent extracelluar calcium influx in HL-60 cells. T 4 could also change apoptotic-related gene expression in leukemic cells, and resulted in the inhibition of proliferation and induction of differentiation and apoptosis of leukemic cells. (c) 2006 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.