title: Cys34-cysteinylated human serum albumin is a sensitive plasma marker in oxidative stress-related chronic diseases.
abstract: The degree of oxidized cysteine (Cys) 34 in human serum albumin (HSA), as determined by high performance liquid chromatography (HPLC), is correlated with oxidative stress related pathological conditions. In order to further characterize the oxidation of Cys34-HSA at the molecular level and to develop a suitable analytical method for a rapid and sensitive clinical laboratory analysis, the use of electrospray ionization time-of-flight mass spectrometer (ESI-TOFMS) was evaluated. A marked increase in the cysteinylation of Cys34 occurs in chronic liver and kidney diseases and diabetes mellitus. A significant positive correlation was observed between the Cys-Cys34-HSA fraction of plasma samples obtained from 229 patients, as determined by ESI-TOFMS, and the degree of oxidized Cys34-HSA determined by HPLC. The Cys-Cys34-HSA fraction was significantly increased with the progression of liver cirrhosis, and was reduced by branched chain amino acids (BCAA) treatment. The changes in the Cys-Cys34-HSA fraction were significantly correlated with the alternations of the plasma levels of advanced oxidized protein products, an oxidative stress marker for proteins. The binding ability of endogenous substances (bilirubin and tryptophan) and drugs (warfarin and diazepam) to HSA purified from chronic liver disease patients were significantly suppressed but significantly improved by BCAA supplementation. Interestingly, the changes in this physiological function of HSA in chronic liver disease were correlated with the Cys-Cys34-HSA fraction. In conclusion, ESI-TOFMS is a suitable high throughput method for the rapid and sensitive quantification of Cys-Cys34-HSA in a large number of samples for evaluating oxidative stress related chronic disease progression or in response to a treatment.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Nagumo
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan.
authors.forename: Motohiko
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: School of Pharmacy, Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia.
authors.forename: Victor Tuan Giam
authors.initials: VT
authors.lastname: Chuang
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Setoyama
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan ; Center for Clinical Pharmaceutical Science, Kumamoto University, Chuo-ku, Kumamoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Institute of Innovation, Ajinomoto Co., Inc., Kawasaki-ku, Kawasaki, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yamada
authors.affiliation: Institute of Innovation, Ajinomoto Co., Inc., Kawasaki-ku, Kawasaki, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kubota
authors.affiliation: Department of Nephrology, Akebono Clinic, Minami-Ku, Kumamoto, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Nephrology, Akebono Clinic, Minami-Ku, Kumamoto, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: Jinnouchi Clinic, Diabetes Care Center, Chuo-ku, Kumamoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshida
authors.affiliation: Jinnouchi Clinic, Diabetes Care Center, Chuo-ku, Kumamoto, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Jinnouchi
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, Nishi-ku, Kumamoto, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Anraku
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan ; Center for Clinical Pharmaceutical Science, Kumamoto University, Chuo-ku, Kumamoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kadowaki
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan ; Center for Clinical Pharmaceutical Science, Kumamoto University, Chuo-ku, Kumamoto, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ishima
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, Nishi-ku, Kumamoto, Japan ; DDS Research Institute, Sojo University, Nishi-ku, Kumamoto, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan ; Center for Clinical Pharmaceutical Science, Kumamoto University, Chuo-ku, Kumamoto, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
mesh_terms: D000368:Aged; D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage; D001663:Bilirubin / Q000737:chemistry; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D003975:Diazepam / Q000737:chemistry; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000178:diet therapy; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011485:Protein Binding; D051437:Renal Insufficiency / Q000097:blood* / Q000175:diagnosis / Q000178:diet therapy; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D014364:Tryptophan / Q000737:chemistry; D014859:Warfarin / Q000737:chemistry
chemical_list: D000597:Amino Acids, Branched-Chain; D015415:Biomarkers; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D014859:Warfarin; D014364:Tryptophan; D003545:Cysteine; D003975:Diazepam; D001663:Bilirubin