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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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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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 / oxidative stress / lipid peroxidation / angiotensin II / 4-oxo-2(E)-nonenal / 4-hydroxy-2(E)-nonenal / mass spectrometry / lipid hydroperoxide |
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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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Report
(4 results)
Research Products
(66 results)
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[Journal Article] A 13-oxo-9,10- epoxytridecenoate phospholipid analogue of the genotoxic 4,5-epoxy-2(E)-decenal: detection in vivo, chemical synthesis, and adduction with DNA2010
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
Chem. Res. Toxicol
Volume: 23
Issue: 3
Pages: 516-27
DOI
Related Report
Peer Reviewed
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[Journal Article] Major biliary bile acids of the Medaka (Oryzias latipes): 25R- and 25S- epimers of 3alpha,7alpha,12alpha- trihydroxy-5beta-cholestanoic acid2010
Author(s)
Hagey, L. R., Lida, T., Tamegai, H., Ogawa, S., Une, M., Asahina, K., Mushiake, K., Goto, T., Mano, N., Goto, J., Krasowski, M. D., Hofmann, A. F.
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Journal Title
Zoolog. Sci
Volume: 27
Issue: 7
Pages: 565-573
DOI
Related Report
Peer Reviewed
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[Journal Article] A 13-oxo-9,10-epoxytridecenoate phospholipid analogue of the genotoxic 4,5-epoxy-2(E)-decenal : detection in vivo, chemical synthesis, and adduction with DNA2010
Author(s)
Clementina Mesaros, Bogdan G.Gugiu, Rong Zhou, Seon Hwa Lee, Jaewoo Choi, James Laird, Ian A.Blair, Robert G.Salomon
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Journal Title
Chemical Research in Toxicology
Volume: Vol.23
Pages: 516-527
Related Report
Peer Reviewed
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[Presentation] Targeted metabolomic analysis of modified angiotensin peptides as potential biomarkers of cardiovascular diseases.2012
Author(s)
Lee, S.H., Takahashi, R., Kojima, S., Suzuki, S., Goto, T., Oe, T.
Organizer
The 60th Annual American Society for Mass Spectrometry(ASMS) Conference
Place of Presentation
Vancouver, Canada
Related Report
Invited
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