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Identification of acrolein-conjugated protein in plasma of patients with brain infarction
Authors:Madoka Yoshida  Kyohei Higashi  Lihua Jin  Takehiro Suzuki  Naoshi Dohmae  Yutaka Tamura  Toshihiko Toida  Keiko Kashiwagi
Affiliation:a Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan
b Amine Pharma Research Institute, Innovation Plaza at Chiba University, 1-8-15 Inohana, Chuo-ku, Chiba 260-0856, Japan
c Biomolecular Characterization Team, RIKEN Advanced Science Institute and CREST, JST, 2-1 Hirosawa, Wako 351-0198, Japan
d Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
e Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba 288-0025, Japan
Abstract:It is known that the level of protein-conjugated acrolein in plasma is a good marker of chronic renal failure and brain infarction. Thus, studies were carried out to determine which kinds of plasma proteins are conjugated with acrolein. It was found that acrolein was mainly conjugated with albumin. Tandem mass spectrometry analysis demonstrated that Lys-557 and Lys-560, located at the surface of domain III of albumin, were the major sites conjugated with acrolein. This is the first report to identify the amino acid residues in a protein modified by acrolein in vivo. It was found that conjugation of acrolein with albumin contributed to a decrease in the toxicity of acrolein.
Keywords:Acrolein   Albumin   MP-lysine   LC-MS/MS   Brain infarction   Renal failure
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