Newman Shelley F, Sultana Rukhsana, Perluigi Marzia, Coccia Rafella, Cai Jian, Pierce William M, Klein Jon B, Turner Delano M, Butterfield D Allan
Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506, USA.
J Neurosci Res. 2007 May 15;85(7):1506-14. doi: 10.1002/jnr.21275.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neurofibrillary tangles, senile plaques, and loss of synapses. Many studies support the notion that oxidative stress plays an important role in AD pathogenesis. Previous studies from our laboratory employed redox proteomics to identify oxidatively modified proteins in the AD inferior parietal lobule (IPL) and hippocampus. The proteins were consistent with biochemical or pathological alterations in AD and have been central to further investigations of the disease. The present study focused on the identification of specific targets of protein S-glutathionylation in AD and control IPL by using a redox proteomics approach. For AD IPL, we identified deoxyhemoglobin, alpha-crystallin B, glyceraldehyde phosphate dehydrogenase (GAPDH), and alpha-enolase as significantly S-glutathionylated relative to these brain proteins in control IPL. GAPDH and alpha-enolase were also shown to have reduced activity in the AD IPL. This study demonstrates that specific proteins are sensitive to S-glutathionylation, which most likely is due to their sensitivity to cysteine oxidation initiated by the increase in oxidative stress in the AD brain.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征为神经原纤维缠结、老年斑和突触丧失。许多研究支持氧化应激在AD发病机制中起重要作用这一观点。我们实验室之前的研究采用氧化还原蛋白质组学来鉴定AD患者顶下小叶（IPL）和海马体中发生氧化修饰的蛋白质。这些蛋白质与AD中的生化或病理改变一致，并且一直是该疾病进一步研究的核心。本研究通过氧化还原蛋白质组学方法，重点鉴定AD患者和对照IPL中蛋白质S-谷胱甘肽化的特定靶点。对于AD患者的IPL，相对于对照IPL中的这些脑蛋白，我们鉴定出脱氧血红蛋白、αB-晶状体蛋白、甘油醛-3-磷酸脱氢酶（GAPDH）和α-烯醇化酶为显著发生S-谷胱甘肽化的蛋白。GAPDH和α-烯醇化酶在AD患者的IPL中也显示出活性降低。这项研究表明特定蛋白质对S-谷胱甘肽化敏感，这很可能是由于它们对AD脑中氧化应激增加引发的半胱氨酸氧化敏感。
