Pedersen W A, Fu W, Keller J N, Markesbery W R, Appel S, Smith R G, Kasarskis E, Mattson M P
Sanders-Brown Research Center on Aging, University of Kentucky, Lexington 40536-0230, USA.
Ann Neurol. 1998 Nov;44(5):819-24. doi: 10.1002/ana.410440518.
We report increased modification of proteins by 4-hydroxynonenal (HNE), a product of membrane lipid peroxidation, in the lumbar spinal cord of sporadic amyotrophic lateral sclerosis (ALS) patients versus that of neurologically normal controls. By immunohistochemistry, HNE-protein modification was detected in ventral horn motor neurons, and immunoprecipitation analysis revealed that one of the proteins modified by HNE was the astrocytic glutamate transporter EAAT2. Given that the function of proteins modified by HNE can be severely compromised as previously demonstrated for glutamate transporters in cortical synaptosome preparations, our findings suggest a scenario in which oxidative stress leads to the production of HNE, impairment of glutamate transport, and excitotoxic motor neuron degeneration in ALS.
我们报告，与神经功能正常的对照组相比，散发性肌萎缩侧索硬化症（ALS）患者的腰脊髓中，由膜脂质过氧化产物4-羟基壬烯醛（HNE）导致的蛋白质修饰增加。通过免疫组织化学方法，在腹角运动神经元中检测到了HNE-蛋白质修饰，免疫沉淀分析显示，被HNE修饰的蛋白质之一是星形胶质细胞谷氨酸转运体EAAT2。鉴于如先前在皮质突触体标本中对谷氨酸转运体所证明的那样，被HNE修饰的蛋白质功能可能会严重受损，我们的研究结果提示了一种情形，即氧化应激导致HNE生成、谷氨酸转运受损以及ALS中兴奋性毒性运动神经元变性。
