C1抑制剂和prolylcarboxypeptidase调节了内皮细胞上的前卡利克林激活
Alona A Merkulova1, Sarah Abdalian2, Sadiq Silbak1
1Hematology and Oncology Division, Department of Medicine, Case Western Reserve University, Cleveland, Ohio.
The Journal of allergy and clinical immunology
|July 3, 2023
概括
在内皮细胞上的前卡利克莱因 (PK) 激活由C1抑制剂 (C1INH) 和prolylcarboxypeptidase (PRCP) 控制. 较高的C1INH水平降低了PK激活和高分子量激素 (HK) 裂变,影响了布拉迪基宁 (BK) 的释放.
科学领域:
- 内皮细胞生物学 内皮细胞生物学
- 卡利克里恩-基宁系统
- 酶学 是一种酶学.
背景情况:
- 人类微血管内皮细胞 (HMVECs) 表达前卡利克莱因 (PK),高分子量激素原 (HK),C1抑制剂 (C1INH) 和prolylcarboxypeptidase (PRCP).
- 通过C1INH和PRCP对内皮细胞PK激活的调节尚未完全理解.
研究的目的:
- 研究C1INH和PRCP度如何调节HMVEC上的PK激活.
- 确定PRCP在PK激活特异性中的作用以及C1INH对HK裂变和布拉迪基宁 (BK) 释放的影响.
主要方法:
- 研究使用培养的HMVECs.
- 技术包括免疫光,酶活性测定,免疫斑块,小干扰RNA (siRNA) 敲击和细胞传染.
主要成果:
- 对HMVECs的PK激活是依赖C1INH的度.
- 在没有C1INH的情况下,激活的PK (PKa) 完全切割了HK; 2μMC1INH减少了50%的HK切割.
- PRCP siRNA的淘汰增强了C1INH的抑制作用,而PRCP转染减少了C1INH的抑制作用.
结论:
- PK 激活和 HK 分裂,导致 BK 在 HMVEC 上释放,由局部 C1INH 和 PRCP 度调节.
- 这些发现阐明了kallikrein-kinin系统在内皮细胞上的复杂调节.
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