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类胰蛋白酶:遗传学及功能方面的考量

Tryptase: genetic and functional considerations.

作者信息

Hernández-Hernández L, Sanz C, García-Solaesa V, Padrón J, García-Sánchez A, Dávila I, Isidoro-García M, Lorente F

机构信息

Department of Immunoallergy, University Hospital of Salamanca, Salamanca, Spain.

出版信息

Allergol Immunopathol (Madr). 2012 Nov-Dec;40(6):385-9. doi: 10.1016/j.aller.2012.04.004. Epub 2012 Jul 4.

Abstract

Tryptase is one of the main proteases located in the secretory granules of the mast cells, and is released through degranulation. It is therefore assumed to play an important role in inflammatory and allergic processes. Four genes are known to encode for these enzymes, with different alleles that give rise to different types of tryptases. The term "tryptase" generally refers to β-tryptase, which in vivo is a heterotetramer, possessing a structure of vital importance for enabling drug and substrate access to the active site of the molecule. Tryptase has been reported to possess antagonistic functions, since it plays an important role both in inflammatory phenomena and as a protector against infection. In allergic processes it is associated to bronchial hyperresponsiveness in asthmatic patients, where PAR-2 is of great importance as an airway receptor. Lastly, the genes that encode for tryptase are highly polymorphic and complex. As a result, it is important to establish a relationship between genotype and phenotype in disorders such as asthma, and to identify mutations that are presumably of pharmacological relevance.

摘要

类胰蛋白酶是位于肥大细胞分泌颗粒中的主要蛋白酶之一,通过脱颗粒释放。因此,它被认为在炎症和过敏过程中起重要作用。已知有四个基因编码这些酶,不同的等位基因产生不同类型的类胰蛋白酶。术语“类胰蛋白酶”通常指β-类胰蛋白酶,其在体内是一种异源四聚体,具有对于使药物和底物能够进入分子活性位点至关重要的结构。据报道,类胰蛋白酶具有拮抗功能,因为它在炎症现象中以及作为抗感染的保护剂都发挥着重要作用。在过敏过程中,它与哮喘患者的支气管高反应性有关,其中PAR-2作为气道受体非常重要。最后,编码类胰蛋白酶的基因具有高度多态性和复杂性。因此,在哮喘等疾病中建立基因型与表型之间的关系,并识别可能具有药理学相关性的突变非常重要。

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