Pathophysiological roles of M1 aminopeptidases
| Project/Area Number |
25293083
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Teikyo Heisei University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TAKASU Kiyosei 京都大学, 薬学研究院, 教授 (10302168)
HATTORI Akira 京都大学, 薬学研究院, 准教授 (50300893)
OGAWA Yuko 帝京平成大学, 薬学部, 准教授 (30267330)
GOTO Yoshikuni 帝京平成大学, 薬学部, 講師 (90455345)
OGAWA Kenji 独立行政法人理化学研究所, 専任研究員 (50251418)
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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 |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | M1アミノペプチダーゼ / 小胞体アミノペプチダーゼ / ノックアウトマウス / 一酸化窒素 / ERAP1 / アルギニン / Toll-様受容体 / MyD88 / カルモジュリン |
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| Outline of Final Research Achievements |
Endoplasmic reticulum aminopeptidase (ERAP)1 was secreted under infectious conditions. When analyzed the mechanism, several cytokines were expressed in macrophages in response to LPS and IFN-gamma and their synergistic action caused the secretion via induction of calcium mobilization. Then we found that ERAP1 contributed to the NO production in vivo when analyzed by employing ERAP1-knockout mice.
In the serum of knockout mice, decrease in free arginine level was observed, suggesting that ERAP1 caused the cleavage of N-terminal arginine of substrate peptides and thus increased NO production. Further works are now in progress to elucidate the pathophysiological roles of ERAP1.
By molecular modeling, we elucidated the characteristic features of the substrate pocket of M1 aminopeptidases. Based on these results, we screened the inhibitor of ERAP1 and found a candidate. After optimization, we will develop a therapeutically useful inhibitor to pathological conditions caused by ERAP1.
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Report
(4 results)
Research Products
(9 results)
