Pandit Ashish, Vadnal Jonathan, Houston Sara, Freeman Ernest, McDonough Jennifer
School of Biomedical Sciences, Kent State University, Kent, OH 44242, USA.
J Neurol Sci. 2009 Apr 15;279(1-2):14-20. doi: 10.1016/j.jns.2009.01.009. Epub 2009 Feb 1.
Multiple sclerosis (MS) is an inflammatory neurodegenerative disease. Recently, decreased expression of nuclear encoded electron transport chain genes was found in neurons in MS cortex. To understand the transcriptional mechanisms responsible for the coordinate down regulation of these genes, we performed electrophoretic mobility shifts with nuclear extracts isolated from gray matter from nonlesion areas of postmortem MS and control cortex. Nine tissue blocks from eight different MS brains and six matched control blocks from five control brains were analyzed. We identified a decrease in a transcription factor complex containing nuclear respiratory factor 2 (NRF-2) in nuclear extracts isolated from MS cortex. This decrease is correlated with decreased expression of electron transport chain subunit genes and increased oxidative damage measured by increased anti-nitrotyrosine immunoreactivity. We conclude that in MS cortex a chronic increase in oxidative stress leads to aberrant regulation of transcription of genes involved in energy metabolism.
多发性硬化症（MS）是一种炎症性神经退行性疾病。最近，在MS皮质的神经元中发现核编码电子传递链基因的表达降低。为了了解负责这些基因协同下调的转录机制，我们用从死后MS和对照皮质的非病变区域灰质中分离的核提取物进行了电泳迁移率变动分析。分析了来自八个不同MS脑的九个组织块和来自五个对照脑的六个匹配对照块。我们发现在从MS皮质分离的核提取物中，含有核呼吸因子2（NRF-2）的转录因子复合物减少。这种减少与电子传递链亚基基因表达降低以及通过抗硝基酪氨酸免疫反应性增加所测量的氧化损伤增加相关。我们得出结论，在MS皮质中，氧化应激的慢性增加导致参与能量代谢的基因转录异常调节。
