Protein Damage in Oxidative Stress and Disease

描述（由申请人提供）：氧化应激是受环境影响的疾病的标志，包括神经退行性疾病、癌症、糖尿病和代谢综合征以及其他炎症相关疾病。虽然反应性亲电试剂和氧化剂可以修饰蛋白质，但由于难以表征来自生命系统的复杂蛋白质组中的修饰，因此难以评估此类蛋白质损伤的具体作用。质谱法和相关蛋白质组分析方法的最新进展使识别损伤靶点成为可能，并为探索疾病机制、探索与环境因素的联系以及开发暴露和影响的生物标志物提供了新的机会。本次研讨会，题为“蛋白质损伤在氧化应激和疾病”将探讨新的工作分析和蛋白质损伤的影响，在神经退行性疾病和糖尿病的背景下。丹尼尔Liebler（研讨会共同主席）将讨论亲和捕获化学和串联质谱的新应用，以进行蛋白质组规模的评估由氧化应激形成的内源性亲电蛋白的蛋白质目标。Harry Ijuropoulos（研讨会联合主席）将描述串联质谱的应用，以表征氧化和硝化应激中涉及的S-亚硝化反应的氧化还原敏感蛋白硫醇靶点，并描述与帕金森病和阿尔茨海默病相关的蛋白靶点的分析。Akira Sawa博士将讨论位点特异性S-亚硝基化反应在触发蛋白质靶点核转位和神经元凋亡中的作用。John Baynes博士将讨论2型糖尿病和代谢综合征的血液蛋白和生物标志物的氧化和糖化修饰分析。最后，维克托Darley-Usmar博士将描述亲电子前列腺素类在位点特异性线粒体蛋白修饰和诱导细胞凋亡中的作用。这些演讲共同代表了分析蛋白质损伤和探索蛋白质损伤作为环境相关疾病原因的最新技术。

DESCRIPTION (provided by applicant): Oxidative stress is a hallmark of environmentally-influenced diseases, including neurodegenerative disorders, cancer, diabetes and metabolic syndrome and other inflammation-related disorders. Although reactive electrophiles and oxidants can modify proteins, the specific role of such protein damage has been difficult to assess because of the difficulty in characterizing modifications in complex proteomes from living systems. Recent advances in mass spectrometry and related proteome analytical approaches make possible the identification of targets of damage and offers new opportunities to explore disease mechanisms, to probe links to environmental factors and to develop biomarkers of exposure and effect. This symposium, entitled "Protein Damage in Oxidative Stress and Disease" will explore new work on the analysis and impact of protein damage in the context of neurodegenerative disease and diabetes. Daniel Liebler (symposium co-Chair) will discuss new applications of affinity capture chemistry and tandem mass spectrometry to perform proteome-scale assessment of protein targets of endogenous electrophiles formed by oxidative stress. Harry Ischiropoulos (symposium co-Chair) will describe the application of tandem mass spectrometry to characterize redox-sensitive protein thiol targets of S-nitrosation reactions involved in oxidative and nitrative stress and describe the analysis of protein targets relevant to Parkinson's and Alzheimer's disease. Dr. Akira Sawa will discuss the roles of site-specific S-nitrosylation reactions in triggering nuclear translocation of the protein targets and neuronal apoptosis. Dr. John Baynes will discuss the analysis of oxidative and glycation modifications of blood proteins and biomarkers for type 2 diabetes and metabolic syndrome. Finally, Dr. Victor Darley-Usmar will describe the roles of electrophilic prostanoids in site-specific mitochondrial protein modification and induction of apoptosis. These presentations collectively represent the state-of-the-art in the analysis protein damage and the exploration of protein damage as a cause of environmentally-related disease.