title: Clinical Implications Associated With the Posttranslational Modification-Induced Functional Impairment of Albumin in Oxidative Stress-Related Diseases.
abstract: Recent research findings indicate that the posttranslational modification of human serum albumin (HSA) such as oxidation, glycation, truncation, dimerization, and carbamylation is related to certain types of diseases. We report herein on a simple and rapid analytical method, using an electrospray ionization time-of-flight mass spectrometry technique, that allows posttranslational modifications of HSA to be quantitatively and qualitatively evaluated with a high degree of sensitivity. In patients with chronic liver disease, chronic renal disease, and diabetes mellitus, an increase in the level of oxidized cysteine-34 (Cys-34) of HSA accompanied by a decrease in the level of reduced Cys-34 was observed. The redox status of Cys-34 was correlated with ligand binding and the antioxidative functions of HSA. Available evidence indicates that monitoring the redox state of Cys-34 not only could be a useful marker for evaluating the progression of disease and its complications but also would permit therapeutic efficacy to be predicted. The redox state of Cys-34 was also used as an index of the quality of HSA preparations. These data suggest that monitoring the posttranslational modifications of HSA can be important, because the function of HSA is related not only to its serum concentration but also to the preservation of its structural integrity under disease conditions.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Center for Clinical Pharmaceutical Sciences, School of Pharmacy, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Imafuku
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0822, Japan; DDS Research Institute, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0822, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Center for Clinical Pharmaceutical Sciences, School of Pharmacy, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. Electronic address: tomaru@gpo.kumamoto-u.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D003545:Cysteine / Q000235:genetics; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D000075462:Serum Albumin, Human / Q000235:genetics*
chemical_list: D003545:Cysteine; D000075462:Serum Albumin, Human
keywords: albumin; biomarker; cysteine-34; diabetes mellitus; kidney disease; ligand binding; liver disease; oxidative stress; posttranslational modification