Basic apoptotic mechanisms of lead toxicity in human leukemia (HL-60) cells.
Basic apoptotic mechanisms of lead toxicity in human leukemia (HL-60) cells.
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DOI：
10.3390/ijerph7052008
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发表时间：
2010-05
影响因子：
--
通讯作者：
Tchounwou PB
中科院分区：
文献类型：
--
作者：
Yedjou CG;Milner JN;Howard CB;Tchounwou PB
铅接触是一种医疗和公共卫生紧急情况，特别是在儿童消费大量铅污染的片状油漆。它还可能对所有年龄段的人造成血液学影响。本实验室最近的研究表明，细胞凋亡可能与铅诱导的氧化应激和DNA损伤有关。然而，其对淋巴细胞作用的机制在很大程度上仍然未知。因此，本研究的目的是探讨硝酸铅[Pb（NO3）2]的HL-60细胞作为测试模型的凋亡机制。用不同浓度的Pb（NO3）2处理HL-60细胞24 h后，进行细胞活力测定和流式细胞术检测。台盼蓝拒染试验结果表明，在很低浓度下，Pb（NO3）2对HL-60细胞的存活率无影响。当暴露于高水平的Pb（NO3）2时，观察到细胞活力显著降低（p <0.05）。从流式细胞术评估产生的数据表明，与对照相比，Pb（NO3）2暴露显著（p <0.05）增加了膜联蛋白V阳性细胞（凋亡细胞）的比例。Pb（NO3）2诱导HL-60细胞凋亡与caspase-3的激活有关。总之，这些研究表明，Pb（NO3）2代表HL-60早幼粒细胞白血病细胞的凋亡诱导剂，其凋亡机制的功能，至少部分通过诱导磷脂酰丝氨酸外化和caspase-3激活。
Lead exposure represents a medical and public health emergency, especially in children consuming high amounts of lead-contaminated flake paints. It may also cause hematological effects to people of all ages. Recent studies in our laboratory have indicated that apoptosis may be associated with the lead-induced oxidative stress and DNA damage. However, the mechanisms underlying its effect on lymphocytes are still largely unknown. Therefore, the aim of the present study was to investigate the apoptotic mechanisms of lead nitrate [Pb(NO3)2] using HL-60 cells as a test model. HL-60 cells were treated with different concentrations of Pb(NO3)2 for 24 h prior to cell viability assay and flow cytometry assessment. The results obtained from the trypan blue exclusion test indicated that at very low concentration, Pb(NO3)2 has no effect on the viability of HL-60 cells. A significant (p < 0.05) decrease in cell viability was observed when exposed to high level of Pb(NO3)2. Data generated from the flow cytometric assessment indicated that Pb(NO3)2 exposure significantly (p < 0.05) increased the proportion of annexin V positive cells (apoptotic cells) compared to the control. Pb(NO3)2 induced apoptosis of HL-60 cells was associated with the activation of caspase-3. In summary, these studies demonstrated that Pb(NO3)2 represents an apoptosis-inducing agent in HL-60 promyelocytic leukemia cells and its apoptotic mechanism functions, at least in part via, induction of phosphatidylserine externalization and caspase-3 activation.
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