在angiotensinogen-Brief报告的距离面保存序列的功能性探索
Naofumi Amioka1,2, Chia-Hua Wu1,3, Hisashi Sawada1,2,4
1Saha Cardiovascular Research Center (N.A., C.-H.W., H.S., S.I., A.C.P., C.W., J.J.M., D.A.H., G.A.G., A.D., H.S.L.), University of Kentucky, Lexington.
血管增生素 (AGT) 保存序列中的突变会影响其从肝细胞分泌出来. 循环和β-sheet区域都对AGT分泌至关重要,影响血压和动脉样硬化.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 心血管研究研究心血管研究
背景情况:
- ангиотензиноген (AGT) 是雷宁- ангиотензин系统的一个关键组成部分.
- 在AGT的循环和β-sheet区域中保存的序列至关重要,但在功能上尚未研究.
研究的目的:
- 为了研究AGT的循环和β-sheet区域中保存序列的功能作用.
- 确定这些保存序列是如何调节肝细胞中AGT分泌的.
主要方法:
- 编码野生型或突变的小鼠AGT的腺相关病毒载体 (AAV) 用于肝细胞特异性AGT缺乏小鼠和HepG2细胞.
- 给小鼠食西方饮食以诱导动脉样硬化.
- 评估了AGT水平,血压和动脉样硬化病变.
主要成果:
- 单个循环或β-sheet区域的突变没有影响AGT分泌,血压或动脉样硬化.
- 这两个区域同时发生的突变导致了AGT在肝细胞中的积累,并使血压和动脉样硬化正常化.
- 肝脏AgtmRNA水平很高,但AGT蛋白在细胞内积累,而不是在ER中.
结论:
- 在AGT的循环和β-sheet区域中保存的序列单独不会影响AGT调节.
- 这些保存的序列协同控制肝细胞中的AGT分泌.
- 破坏这两个保护区域会损害AGT分泌,提供潜在的治疗点.
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