Lipid hydroperoxide-derived modifications to neuropeptides: a novel approach for neurodegenerative diseases

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460186
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Tohoku University
• Principal Investigator: LEE SEON HWA 東北大学, 薬学研究科(研究院), 助教 (60519776)
• Co-Investigator(Kenkyū-buntansha): Oe Tomoyuki 東北大学, 大学院薬学研究科, 教授 (10203712)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: Oxidative stress / Lipid peroxidation / Chemical modification / Mass spectrometry / Angiotensin peptides / Neuropeptides

Outline of Final Research Achievements

In the reactions of angiotensin (Ang) II with lipid peroxidation-derived 4,5-epoxy-2(E)-decenal or 4-hydroperoxy-2(E)-nonenal, the major modifications have been identified at the N-terminus and His6 of Ang II. 4-Oxo-2(E)-nonenal was shown to introduce an α-ketoamide moiety at the N-terminus of Ang peptides containing not only N-terminal Asp but also Ala, Arg and Val. The resulting N-terminal α-ketoamide is converted to the D- and L-amino acids by transamination in the presence of pyridoxamine. The reaction of Ang II and the hydroxyl radical produced N-terminal cyclized-Ang II (Ang C) as well as pyruvamide-Ang II (Ang P). Ang P and Ang C were not further metabolized by aminopeptidase A, which converts Ang II to Ang III. Formation and transamination of N-terminal α-ketoamide, and N-terminal cyclization were also observed in neuropeptides including amyloid beta 1-11. Analytical conditions were optimized to detect N-terminal α-ketoamide Ang peptides in human plasma.

Free Research Field

医歯薬学