| Project/Area Number |
25460186
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
LEE SEON HWA 東北大学, 薬学研究科(研究院), 助教 (60519776)
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| Co-Investigator(Kenkyū-buntansha) |
Oe Tomoyuki 東北大学, 大学院薬学研究科, 教授 (10203712)
後藤 貴章 東北大学, 薬学研究科(研究院), 講師 (40344684)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Oxidative stress / Lipid peroxidation / Chemical modification / Mass spectrometry / Angiotensin peptides / Neuropeptides / oxidative stress / lipid peroxidation / angiotensin II / EDE / HPNE / mass spectrometry / Hydroxyl radical |
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| 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.
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