2012 Fiscal Year Final Research Report
Lipid hydroperoxide-derived modifications to angiotensin peptides:a novel approach for cardiovascular disease
| Project/Area Number |
22590130
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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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, 大学院・薬学研究科, 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)
GOTO Takaaki 東北大学, 大学院・薬学研究科, 講師 (40344684)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 臨床化学 / 酸化ストレス / 化学修飾 / アンジオテンシン |
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| Research Abstract |
In the reactions of angiotensin (Ang) II with lipid peroxidation-derived bifunctional electrophiles, 4-oxo-2(E)-nonenal (ONE) or 4-hydroxy-2(E)-nonenal (HNE), the major modifications have been identified at the N-terminus, Asp^1, Arg^2, and His^6 of Ang II. The identities of ONE- and HNE-modified Ang IIs were confirmed by mass spectrometry (MS) before and after the reaction with sodium borohydride. A novel ONE-derive pyruvamide-Ang II was formed via oxidative decarboxylation of N-terminal aspartic acid. The unexpected formations of Arg- and His- modifications were confirmed using model reactions with N^α-tert-butoxycarbonyl-amino acids. To investigate the biological effects of modified Ang IIs, MS-based label-free Ang II type 1 (AT_1) receptor binding assay and aminopeptidase (AP) A enzyme assay have been developed. Using these methodologies, we have confirmed that the oxidative modifications on the N-terminus of Ang II disrupt interactions with AT_1 receptor and APA, which could affect the regulation of cardiovascular function.
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Author(s)
Mesaros, C., Gugiu, B.G., Zhou, R., Lee, S.H., Choi, J., Laird, J., Blair, I.A., Salomon, R.G.
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Journal Title
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Volume: 23
Pages: 516-27
DOI
Peer Reviewed
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Author(s)
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Journal Title
Zoolog. Sci
Volume: 27
Pages: 565-573
DOI
Peer Reviewed
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