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Regulation and Physiological Roles of Human Tryptase in the Secretary Granules of Mast Cells

人类胰蛋白酶在肥大细胞秘书颗粒中的调控及生理作用

基本信息

批准号：
09680624
负责人：
SAKAI Kentaro
金额：
$ 1.34万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680624/
关键词：
Tryptase Mast Cells Human

项目摘要

The human tryptase family is selectively expressed in mast cells. Products of β-tryptase gene (s) are autocatalytically processed from the pro- to the pro' enzyme at acidic pH in the presence of heparin proteoglycan, from the pro' to the mature peptide at acidic pH by dipeptidyl peptidase I, and to the enzymatically active tetramer by spontaneous conformational alterations at acidic pH in the presence of heparin. Β-Tryptase is stabilized at acidic pH by heparin, and is resistant to biologic inhibitors of serine proteases. In the absence heparin, β-tryptase spontaneously inactivates at neutral pH as it forms monomers, while at acidic pH the inactive monomers spontaneously re-form the active tetramer both in the presence and in the absence of heparin. The optimal pH for tetramer formation and reactivation is about 6, sugessting His residues play a critical role. Whether these physicochemical properties of the enzyme relate to how it is regulated in vivo is uncertain. In this regard, human β-tryptase was found to have an acidic pH optimum for cleavage of heparin proteoglycan and C3, as well as for autoprocessing. This property might restrict optimal activity in vivo to tisse or mucosal sites with an acidic pH, such as sites of inflammation and wound healing, or such as the airway. Whether reactivation of human β-tryptase occurs at extracellular or intracellular sites, where the pH is acidic in vivo, should be considered.

人类胰蛋白酶家族在肥大细胞中选择性表达。β-胰蛋白酶基因的产物在酸pH条件下，在肝素蛋白聚糖存在下，由前-酶自动催化转化为前‘酶；在酸pH条件下，由二肽基肽酶I从前’酶转化为成熟肽；在酸pH条件下，在肝素存在下，由自发构象改变转化为酶活性四聚体。Β-Tryptase通过肝素在酸性pH下稳定，并且对丝氨酸蛋白酶的生物抑制剂具有抗性。在没有肝素的情况下，β-胰蛋白酶在中性pH下自发失活，因为它形成了单体，而在酸性pH下，失活的单体在存在和不存在肝素的情况下都自发地重新形成了活性的四聚体。四聚体形成和再激活的最佳pH约为6，表明他的残基起关键作用。酶的这些物理化学性质是否与它在体内的调节方式有关尚不确定。在这方面，人类β-胰蛋白酶被发现具有最适合肝素蛋白多糖和C3切割以及自动加工的酸性pH值。这种特性可能会限制体内最佳活性在pH值为酸性的组织或粘膜部位，如炎症和伤口愈合部位，或气道。应该考虑人β-胰蛋白酶的再激活是否发生在细胞外或细胞内，在体内pH值为酸性的地方。