Protein Damage in Oxidative Stress and Disease

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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.