AJPR276 - Oxidized amino acids in the urine of aging rats:...

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Oxidized amino acids in the urine of aging rats: potential markers for assessing oxidative stress in vivo CHRISTIAAN LEEUWENBURGH, 1 POLLY A. HANSEN, 1 JOHN O. HOLLOSZY, 1 AND JAY W. HEINECKE 1,2 Departments of 1 Internal Medicine and 2 Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110 Leeuwenburgh, Christiaan, PollyA. Hansen, John O. Holloszy, and Jay W. Heinecke. Oxidized amino acids in the urine of aging rats: potential markers for assessing oxidative stress in vivo. Am. J. Physiol. 276 ( Regulatory Integrative Comp. Physiol. 45): R128–R135, 1999.—Oxida- tive damage of proteins has been implicated in disease and aging. In vitro studies demonstrate that two unnatural amino acids, o,o 8 -dityrosine and o -tyrosine, are stable markers of protein oxidation. We have investigated the possibility that assaying these compounds in urine could provide a noninva- sive way to determine levels of protein oxidation in vivo. Isotope dilution gas chromatography-mass spectrometry was used to quantify levels of o,o 8 -dityrosine and o -tyrosine in skeletal muscle and urine of aging rats subjected to two interventions: 1 ) dietary antioxidant supplementation and 2 ) exercise training. In both sedentary rats and exercise-trained rats, antioxidant therapy reduced levels of protein-bound o,o 8 -dityrosine in skeletal muscle. In contrast, antioxidant therapy or exercise training minimally affected o -tyrosine levels in this tissue. Levels of the oxidized amino acids in urine samples mirrored those of skeletal muscle proteins. Quantification of the levels of oxidized amino acids in urine may thus serve as a noninvasive measure of oxidative stress in vivo because they change in parallel with levels of protein- bound oxidized amino acids in skeletal muscle. o,o 8 -dityrosine; ortho-tyrosine; antioxidants; exercise; protein oxidation OXIDATIVE DAMAGE OF proteins, lipids, and nucleic acids has been implicated in diseases ranging from atheroscle- rosis to ischemia-reperfusion injury to cancer (1–3, 16, 32). Many lines of evidence also suggest that such damage plays a causal role in aging (1–3, 23, 28, 33, 34). One important target may be proteins (3, 33), which play fundamental roles as biological catalysts, gene regulators, and structural components of cells. One widely studied model of protein oxidation involves metal-catalyzed reactions that generate hydroxyl radi- cal and other reactive species. These oxidants generate reactive carbonyls from certain amino acid residues (3, 23, 33). The discovery of elevated levels of protein carbonyls in many pathological states (3) and in tissues of old animals (3, 28, 33, 34) has implicated protein oxidation in the pathogenesis of disease and aging. A major difficulty in evaluating the roles of oxidants in human disease has been the lack of precise measures of oxidative stress in vivo (7). Many of the currently available methods are nonspecific and prone to arti- facts. A powerful approach to studying oxidative dam- age in vivo is the analysis of normal and diseased tissue for specific markers (9, 21, 26, 30, 31). Such markers
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AJPR276 - Oxidized amino acids in the urine of aging rats:...

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