Human apurinic/apyrimidinic endonuclease 1 translocalizes to mitochondria after photodynamic therapy and protects cells from apoptosis
Human apurinic/apyrimidinic endonuclease 1 translocalizes to mitochondria after photodynamic therapy and protects cells from apoptosis
复制标题
光动力治疗后人无嘌呤/无嘧啶核酸内切酶 1 转定位至线粒体并保护细胞免于凋亡
DOI：
10.1111/j.1349-7006.2012.02239.x
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发表时间：
2012-05-01
期刊：
影响因子：
5.7
通讯作者：
Yang, Zhen-Zhou
中科院分区：
文献类型：
--
作者：
Li, Meng-Xia;Shan, Jin-Lu;Yang, Zhen-Zhou
光动力学疗法（PDT）是治疗肺癌的有效方法。线粒体功能衰竭被认为是PDT后导致细胞死亡的最重要因素之一。然而，所涉及的详细机制仍不清楚。我们以前报道过，脱嘌呤/脱嘧啶核酸内切酶（APE 1）在调节肺癌A549细胞系对PDT的敏感性中起着关键作用。最近报道了APE 1的重要线粒体调节作用，因此我们通过调节线粒体功能探索了APE 1在PDT诱导的氧化应激后细胞存活中的作用。我们首先观察到，光照射诱导APE 1的线粒体易位。在APE 1敲低的A549细胞中检测APE 1调节光照射后线粒体膜电位和活性氧（ROS）产生的能力。APE 1缺陷型A549细胞的特征是具有较低的线粒体膜电位和较高的ROS产生，这导致PDT后通过线粒体途径的凋亡增加。此外，在线粒体中观察到APE 1的意外活性：通过线粒体转录因子A（TFAM）的氧化还原调节来控制线粒体转录活性。此外，APE 1的两个显性负突变体被过表达以增强其在线粒体中的个体活性。结果表明，这两种APE 1活性在线粒体功能的调节中发挥作用，但通过不同的机制。本研究不仅提供了APE 1调节光照射后存活的可能机制，而且揭示了APE 1在线粒体中的一种新活性。（Cancer Sci 2012; 103：882-888）
Photodynamic therapy (PDT) is an effective therapeutic regime for lung cancer. Mitochondrial functional failure is considered to be one of the most important factors causing cell death after PDT. However, the detailed mechanisms that are involved are still unclear. We previously reported that apurinic/apyrimidinic endonuclease (APE1) plays a critical role in regulating sensitivity to PDT in the lung cancer A549 cell line. An important mitochondrial regulatory role for APE1 has recently been reported, so therefore we explored the role of APE1 in cell survival after PDT‐induced oxidative stress through regulation of mitochondrial function. We first observed that photoirradiation induced the mitochondrial translocation of APE1. The ability of APE1 to regulate mitochondrial membrane potential and reactive oxygen species (ROS) production after photoirradiation was tested in APE1 knockdown A549 cells. APE1‐deficient A549 cells were characterized as having a lower mitochondrial membrane potential and higher ROS production, which led to increased apoptosis through the mitochondrial pathway after PDT. Additionally, unexpected activity of APE1 was observed in mitochondria: the control of mitochondrial transcriptional activity by redox regulation of mitochondrial transcription factor A (TFAM). Furthermore, two dominant‐negative mutants of APE1 were overexpressed to enhance their individual activities in mitochondria. The results suggest that both these APE1 activities play a role in the regulation of mitochondrial function but through different mechanisms. The present study not only provides possible mechanisms for APE1 in regulating survival after photoirradiation but also uncovers a new activity of APE1 in mitochondria. (Cancer Sci 2012; 103: 882–888)