| Project/Area Number |
24659153
|
|---|
| Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | Teikyo Heisei University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HATTORI Akira 京都大学, 薬学研究院, 准教授 (50300893)
GOTO Yoshikuni 帝京平成大学, 薬学部, 講師 (90455345)
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | 小胞体アミノペプチダーゼ / マクロファージ / インターフェロン / LPS / 高血圧症 / 一酸化窒素 / NO産生 |
|---|
| Outline of Final Research Achievements |
Endoplasmic reticulum aminopeptidase (ERAP) 1 is secreted from macrophages in response to IFN-γ and LPS, suggesting that it can regulate blood pressure via cleavage of peptide hormones in the blood vessels and thus affect the formation of atherosclerosis.
In this study, we initially analyzed the secretion mechanism of ERAP1. We found that IFN-γ/LPS treatment caused the expression of several cytokines in macrophages such as IFN-β and TNF-α. Synergistic action of these cytokines induced the mobilization of calcium in the cytosol to cause the ERAP1 secretion. We also found that secreted ERAP1 mediated NO production via cleavage of peptide hormones having N-terminal arginine. Taken together, our data suggest that ERAP1 was secreted via calcium mobilization in the cytosol in response to infectious states caused by either bacteria or virus infection and could regulate blood pressure via cleavage of peptide hormones and thus might play roles in the formation of atherosclerosis.
|
