title: Quantitative determination of ortho- and meta-tyrosine as biomarkers of protein oxidative damage in beta-thalassemia.
abstract: Oxidative stress in thalassemia is caused by secondary iron overload and stems from blood transfusion and increased iron uptake. In this study, we hypothesized that levels of o- and m-tyrosine, products of hydroxyl radical attack on phenylalanine, would be elevated in beta-thalassemia (intermediate). This study represents the first report in which specific markers of protein oxidative damage have been quantified in thalassemia. We used GC/MS to assay o- and m-tyrosine at the femtomole level using only a few microliters of plasma. Levels of both markers were significantly higher in patients with beta-thalassemia than in controls and were positively correlated with serum ferritin, malondialdehyde, superoxide dismutase, glutathione peroxidase and glutathione. We conclude that o- and m-tyrosine are useful biomarkers of oxidative damage to proteins in thalassemia (intermediate) and may also be useful markers in other iron overload diseases. Positive correlations between o- and m-tyrosine levels and malondialdehyde as well as antioxidants such as superoxide dismutase, glutathione peroxidase and glutathione, are indicative of the broad impact of oxidative stress on blood plasma in thalassemia, with up-regulation of antioxidant proteins probably reflecting a homeostatic response to these increased stress levels.
authors.affiliation: Department of Chemistry, Faculty of Science, Mahidol University, Bangkok, Thailand. pycmt@mahidol.ac.th
authors.forename: Chutima
authors.initials: C
authors.lastname: Matayatsuk
authors.forename: Anne
authors.initials: A
authors.lastname: Poljak
authors.forename: Sonia
authors.initials: S
authors.lastname: Bustamante
authors.forename: George A
authors.initials: GA
authors.lastname: Smythe
authors.forename: Ruchaneekorn W
authors.initials: RW
authors.lastname: Kalpravidh
authors.forename: Pornpan
authors.initials: P
authors.lastname: Sirankapracha
authors.forename: Suthat
authors.initials: S
authors.lastname: Fucharoen
authors.forename: Prapin
authors.initials: P
authors.lastname: Wilairat
mesh_terms: D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers; D005260:Female; D006801:Humans; D007501:Iron / Q000097:blood; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism*; D014443:Tyrosine / Q000097:blood*; D017086:beta-Thalassemia / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D011506:Proteins; D014443:Tyrosine; C026741:2-tyrosine; C015566:3-tyrosine; D007501:Iron; D001663:Bilirubin