The hypoxic preconditioning agent deferoxamine induces poly(ADP-ribose) polymerase-1-dependent inhibition of the mitochondrial respiratory chain
The hypoxic preconditioning agent deferoxamine induces poly(ADP-ribose) polymerase-1-dependent inhibition of the mitochondrial respiratory chain
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DOI：
10.1007/s11010-011-1162-1
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发表时间：
2012-04-01
影响因子：
4.3
通讯作者：
Siles, Eva
中科院分区：
文献类型：
--
作者：
Canuelo, Ana;Martinez-Romero, Ruben;Siles, Eva
我们以前报道过，单剂量的去铁胺（DFO）作为一种缺氧模拟剂，仅在聚（ADP-核糖）聚合酶（PARP-1）存在下诱导活性氧（ROS）的产生。鉴于线粒体是ROS的主要来源之一，本研究旨在评估DFO处理对线粒体呼吸链复合物活性的影响，更重要的是，确定这种影响是否受PARP-1调节。我们发现DFO处理诱导复合物II和IV活性的进行性下降，但这种活性在PARP-1敲除细胞中得以保留，表明这种下降是由PARP-1介导的。我们还证实，DFO处理后的复合物II抑制与聚ADP核糖基化平行发生。因此，我们建议在使用DFO作为低氧模拟剂时考虑PARP-1激活，因为它介导线粒体呼吸链的改变。
We previously reported that treatment with a single dose of deferoxamine (DFO), which acts as a hypoxic-mimetic agent, only induces reactive oxygen species (ROS) production in the presence of poly(ADP-ribose) polymerase (PARP-1). Given that mitochondria are one of the main sources of ROS, the present study was designed to assess the effect of DFO treatment on the activity of mitochondrial respiratory chain complexes, and more importantly, to determine whether this effect is modulated by PARP-1. We found that DFO treatment induced a progressive decline in complex II and IV activity, but that this activity was preserved in PARP-1 knock-out cells, demonstrating that this decrease is mediated by PARP-1. We also confirmed that complex II inhibition after DFO treatment occurs in parallel with poly-ADP ribosylation. Consequently, we recommend that PARP-1 activation be taken into account when using DFO as a hypoxia-mimetic agent, because it mediates alteration of the mitochondrial respiratory chain.