title: Methionine sulfoxides in serum proteins as potential clinical biomarkers of oxidative stress.
abstract: Oxidative stress contributes to the pathophysiology of a variety of diseases, and circulating biomarkers of its severity remains a topic of great interest for researchers. Our peptidomic strategy enables accurate and reproducible analysis of circulating proteins/peptides with or without post-translational modifications. Conventional wisdom holds that hydrophobic methionines exposed to an aqueous environment or experimental handling procedures are vulnerable to oxidation. However, we show that the mass spectra intensity ratio of oxidized to non-oxidized methionine residues in serum tryptic proteins can be accurately quantified using a single drop of human serum and give stable and reproducible results. Our data demonstrate that two methionine residues in serum albumin (Met-111 and Met-147) are highly oxidized to methionine sulfoxide in patients with diabetes and renal failure and in healthy smokers versus non-smoker controls. This label-free mass spectrometry approach to quantify redox changes in methionine residues should facilitate the identification of additional circulating biomarkers suitable for predicting the development or progression of human diseases.
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.|Laboratory of Biophysics, Department of Physics, Kitasato University School of Science, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.|Center for Disease Proteomics, Kitasato University School of Science, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Laboratory of Biophysics, Department of Physics, Kitasato University School of Science, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.|Center for Disease Proteomics, Kitasato University School of Science, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kodera
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.|Laboratory of Biophysics, Department of Physics, Kitasato University School of Science, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.|Center for Disease Proteomics, Kitasato University School of Science, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.|Laboratory of Biophysics, Department of Physics, Kitasato University School of Science, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.|Center for Disease Proteomics, Kitasato University School of Science, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Momozono
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Hayashi
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kamata
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Shichiri
mesh_terms: D015415:Biomarkers / Q000097:blood* / Q000737:chemistry; D001798:Blood Proteins / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry; D008715:Methionine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012709:Serum Albumin / Q000737:chemistry
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D012709:Serum Albumin; D008715:Methionine; C013111:methionine sulfoxide