College of Pharmacy, Ajou University, Suwon, 443-749, Korea.
Mol Cells. 2013 Sep;36(3):258-66. doi: 10.1007/s10059-013-0172-0. Epub 2013 Aug 29.
Poly(ADP-ribose) polymerase-1 (PARP-1) mediates neuronal cell death in a variety of pathological conditions involving severe DNA damage. Poly(ADP-ribose) (PAR) polymer is a product synthesized by PARP-1. Previous studies suggest that PAR polymer heralds mitochondrial apoptosis-inducing factor (AIF) release and thereby, signals neuronal cell death. However, the details of the effects of PAR polymer on mitochondria remain to be elucidated. Here we report the effects of PAR polymer on mitochondria in cells in situ and isolated brain mitochondria in vitro. We found that PAR polymer causes depolarization of mitochondrial membrane potential and opening of the mitochondrial permeability transition pore early after injury. Furthermore, PAR polymer specifically induces AIF release, but not cytochrome c from isolated brain mitochondria. These data suggest PAR polymer as an endogenous mitochondrial toxin and will further our understanding of the PARP-1-dependent neuronal cell death paradigm.
聚（ADP-核糖）聚合酶-1（PARP-1）在多种涉及严重 DNA 损伤的病理条件下介导神经元细胞死亡。聚（ADP-核糖）（PAR）聚合物是由 PARP-1 合成的产物。先前的研究表明，PAR 聚合物预示着线粒体凋亡诱导因子（AIF）的释放，从而发出神经元细胞死亡的信号。然而，PAR 聚合物对线粒体的影响的细节仍有待阐明。在这里，我们报告了 PAR 聚合物对原位细胞和体外分离的脑线粒体中线粒体的影响。我们发现，PAR 聚合物在损伤后早期引起线粒体膜电位去极化和线粒体通透性转换孔开放。此外，PAR 聚合物特异性诱导 AIF 释放，但不诱导细胞色素 c 从分离的脑线粒体中释放。这些数据表明 PAR 聚合物是一种内源性线粒体毒素，并将进一步加深我们对 PARP-1 依赖性神经元细胞死亡模式的理解。
