Murakami Tetsuro, Nagai Makiko, Miyazaki Kazunori, Morimoto Nobutoshi, Ohta Yasuyuki, Kurata Tomoko, Takehisa Yasushi, Kamiya Tatsushi, Abe Koji
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Brain Res. 2007 May 30;1150:182-9. doi: 10.1016/j.brainres.2007.02.057. Epub 2007 Mar 1.
Growing evidence has recently shown that mutant SOD1 accumulate in the mitochondria and cause vacuolation in transgenic mice carrying mutant SOD1, an animal model of amyotrophic lateral sclerosis (ALS). In this study, the expressions of DNA repair enzymes, oxoguanine glycosylase 1 (ogg1), DNA polymerase beta (polbeta), and DNA polymerase gamma (polgamma) were examined in transgenic mice with an ALS-linked mutant SOD1 gene, a valuable model for human ALS. In presymptomatic Tg mice, the nuclear form of ogg1 was upregulated, whereas mitochondrial ogg1 remained at the same level. DNA polymerase was selectively downregulated in the mitochondria. This study suggests an impaired protective mechanism against oxidative stress in mitochondria. The expressions of these enzymes are predominant in spinal motor neurons, suggesting a mechanism of selective motor neuron death in this animal model of ALS.
最近越来越多的证据表明，突变型超氧化物歧化酶1（SOD1）在线粒体中积累，并在携带突变型SOD1的转基因小鼠（肌萎缩侧索硬化症（ALS）的动物模型）中导致空泡形成。在本研究中，检测了具有与ALS相关的突变型SOD1基因的转基因小鼠（一种对人类ALS有价值的模型）中DNA修复酶、氧化鸟嘌呤糖基化酶1（ogg1）、DNA聚合酶β（polbeta）和DNA聚合酶γ（polgamma）的表达。在症状前的转基因小鼠中，ogg1的核形式上调，而线粒体中的ogg1保持在相同水平。DNA聚合酶在线粒体中被选择性下调。这项研究表明线粒体中针对氧化应激的保护机制受损。这些酶的表达在脊髓运动神经元中占主导地位，提示了在这种ALS动物模型中选择性运动神经元死亡的机制。
