Chao J, Chao L
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425, USA.
Biol Chem Hoppe Seyler. 1995 Dec;376(12):705-13.
Components of the tissue kallikrein-kinin system include tissue kallikrein, kallistatin (kallikrein-binding protein), kininogen, kinin, bradykinin B1 and B2 receptors, and kininases. Tissue kallikrein is a serine proteinase which is capable of cleaving kininogen substrate to release the vasoactive kinin peptide. The binding of kinin to its specific receptor at target organs can produce a wide spectrum of biological effects. Kinin generation is primarily determined by the activity and availability of kallikrein since the level of kininogen is not a rate-limiting factor. Kallikrein levels are controlled by its rate of synthesis, activation, inactivation and clearance. The synthesis of tissue kallikrein is regulated transcriptionally, and its activity is regulated through post-translational processing and inactivation by inhibitors. Kallistatin is a newly discovered serine proteinase inhibitor (serpin) which forms a specific and covalently-linked complex with tissue kallikrein. Kallistatin may regulate tissue kallikrein's activity, bioavailability and clearance rate at the post-translational level. The major site of kallistatin synthesis is the liver with lower expression levels in the pancreas and kidney. Unlike many other serpins which are only present in the plasma, kallistatin is found in various tissues, cells and bodily fluids. The fact that both tissue kallikrein and kallistatin are widely distributed in tissues suggests kallistatin's role as a potential regulator of kallikrein outside the circulation. Protein purification and molecular cloning techniques have been used to study the structure, regulation and function of the components of the kallikrein-kinin system and for exploring their roles in ion transport, inflammation and blood pressure regulation. Considerable progress has been made in recent years to achieve these goals. This article provides an overview of the biochemical properties and potential physiological and pathophysiological roles of kallistatin.
组织激肽释放酶 - 激肽系统的组成成分包括组织激肽释放酶、激肽抑制蛋白（激肽释放酶结合蛋白）、激肽原、激肽、缓激肽B1和B2受体以及激肽酶。组织激肽释放酶是一种丝氨酸蛋白酶，能够切割激肽原底物以释放血管活性激肽肽。激肽与其在靶器官上的特异性受体结合可产生广泛的生物学效应。激肽的生成主要由激肽释放酶的活性和可利用性决定，因为激肽原水平不是限速因素。激肽释放酶水平受其合成、激活、失活和清除速率的控制。组织激肽释放酶的合成受转录调控，其活性通过翻译后加工和抑制剂失活来调节。激肽抑制蛋白是一种新发现的丝氨酸蛋白酶抑制剂（丝氨酸蛋白酶抑制剂），它与组织激肽释放酶形成特异性的共价连接复合物。激肽抑制蛋白可能在翻译后水平调节组织激肽释放酶的活性、生物利用度和清除率。激肽抑制蛋白的主要合成部位是肝脏，在胰腺和肾脏中的表达水平较低。与许多仅存在于血浆中的其他丝氨酸蛋白酶抑制剂不同，激肽抑制蛋白存在于各种组织、细胞和体液中。组织激肽释放酶和激肽抑制蛋白都广泛分布于组织中，这一事实表明激肽抑制蛋白在循环外作为激肽释放酶潜在调节剂的作用。蛋白质纯化和分子克隆技术已被用于研究激肽释放酶 - 激肽系统各成分的结构、调节和功能，并探索它们在离子转运、炎症和血压调节中的作用。近年来在实现这些目标方面取得了相当大的进展。本文概述了激肽抑制蛋白的生化特性以及潜在的生理和病理生理作用。
