| Project/Area Number |
22590130
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Medical pharmacy
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
LEE Seon hwa 東北大学, 大学院・薬学研究科, 助教 (60519776)
|
|---|
| 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)
|
|---|
| Project Period (FY) |
2010 – 2012
|
| Project Status |
Completed (Fiscal Year 2012)
|
| 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)
|
|---|
| 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 |
|---|
| 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.
|
