The effect of H2O2 and tertiary butyl hydroperoxide upon a murine immortal lens epithelial cell line, αTN4-1

The effect of H2O2 and tertiary butyl hydroperoxide upon a murine immortal lens epithelial cell line, αTN4-1
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DOI:
10.1006/exer.2002.2045
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发表时间:
2002-11-01
影响因子:
3.4
通讯作者:
Kleiman, NJ
Kleiman, NJ
中科院分区:
医学3区
文献类型:
--
作者:
Spector, A;Ma, WC;Kleiman, NJ

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过氧化氢和叔丁基过氧化氢(thbhp)浓度相当的影响对不朽小鼠晶状体上皮细胞系进行了研究,作为描述这些过氧化物导致细胞死亡的机制差异的持续努力的一部分。这两种化合物都能在24小时内导致正常的非条件细胞死亡。结果发现,在相似的条件下,TBHP条件下的α - n4 -1细胞在H2O2胁迫下存活,而H2O2条件下的细胞被TBHP杀死。为了更好地理解这些过氧化物是如何起作用的,我们研究了它们对非条件细胞的影响。这两种过氧化物都会导致GSH的快速损失和泵活性的破坏,如c -14-胆碱运输和Rb-86摄取所示。虽然H2O2暴露会导致广泛的DNA损伤,但TBHP的影响很小。H2O2引起的DNA损伤可激活聚adp -核糖基聚合酶(PARP),导致NAD和ATP的耗竭。添加PARP抑制剂3-氨基苯甲酰胺(3AB)可以延缓H2O2诱导的细胞死亡。3AB的存在也维持了H2O2作用下细胞中的AtP水平。H2O2胁迫也破坏了糖酵解和线粒体活性,但这些参数不受TBHP的影响。在这项工作中使用的相对温和的条件下,TBHP诱导的细胞死亡似乎是由膜破坏和还原环境的丧失引起的。(C) 2002年Elsevier Science Ltd.出版
The effect of comparable concentrations of H2O2 and tertiary butyl hydroperoxide (TBHP) upon an immortal murine lens epithelial cell line was examined as part of an ongoing effort to delineate differences in the mechanism by which these peroxides cause cell death. Both compounds result in cell death of normal, unconditioned cells within 24 hr. It was found that with similar conditions, TBHP conditioned alphaTN4-1 cells survive H2O2 stress while H2O2 conditioned cells are killed by TBHP. To better understand how these peroxides act, their effect upon un-conditioned cells has been investigated. Both peroxides cause a rapid loss of GSH and disruption of pump activity as illustrated by C-14-choline transport and Rb-86 uptake. While H2O2 exposure resulted in extensive DNA damage, TBHP had a minimal effect. DNA damage caused by H2O2 was shown to activate polyADP-ribosyl polymerase (PARP), leading to depletion of NAD and ATP. H2O2 induced cell death could be delayed by addition of 3-aminobenzamide (3AB), an inhibitor of PARP. AtP levels in cells subjected to H2O2 were also maintained by the presence of 3AB. H2O2 stress also disrupted glycolysis and mitochondrial activity but these parameters were not affected by TBHP. TBHP induced cell death, under the relatively mild conditions used in this work, appears to be caused by membrane disruption and loss of a reducing environment. (C) 2002 Published by Elsevier Science Ltd.