Oxidative Stress

Mass Spectrometry Group

Cumulative oxidative damage to tissues has been implicated in a number of disease states, e.g. the aging process, cancer, and ischemia reperfusion. The study of oxidative stress in the mitochondria has shown that hydrogen peroxide is produced via the incomplete reduction of oxygen during oxidative phosphorylation. Hydrogen peroxide levels are kept relatively low under normal physiological conditions. Under certain conditions, such as inflammation, excessive amounts of hydrogen peroxide is thought to precede several occurrences, such as lipid peroxidation, DNA and/or protein damage, and glutathione depletion, that are characteristic of oxidative stress.

The role of free radicals in oxidative stress has led to an increased interest in the study of free radicals and their reactions. Reactive oxygen metabolites can interact with cellular constituents, including DNA/RNA, proteins, and unsaturated lipids. Previous studies have suggested that hemoproteins may be involved in redox reactions which contribute to tissue and/or organ damage via reaction with hydrogen peroxide. In addition, a recent study has reported evidence for the association between nitrotyrosine levels and coronary artery disease. Thus, the determination and characterization of protein radical intermediates is important in understanding the mechanisms of these reactions and their contributions to human diseases.

Led by L. Deterding, Ph.D., Staff Scientist, the Mass Spectrometry Workgroup has had a long-term collaboration with the Free Radical Metabolites Group led by R. Mason, Ph.D., in the Laboratory of Pharmacology & Chemistry. The goal of this collaboration is to gain insight on the mechanisms of oxidative stress using a combination of spin trapping of oxidatively-induced free-radicals followed by structural characterization using mass spectrometry.