Role of chitotriosidase (chitinase 1) under normal and disease conditions.

Manasa Kanneganti, Alan Kamba, Emiko Mizoguchi
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引用次数: 110

Abstract

Mammalian chitinases belong to the glycosyl hydrolase 18 family based on structural homology and the family includes a large number of bacterial and eukaryotic chitinases. Among the mammalian chitinases, chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase) are capable of hydrolyzing the β-(1, 4)-linkage between the adjacent N-acetyl glucosamine residues of chitin. CHIT1 is one of the most abundantly secreted proteins, being mainly produced by activated macrophages and epithelial cells. CHIT1 plays a pivotal role in the context of infectious disease including malaria and fungi infections as a host defense towards chitin in pathogen's cell structure and as a diagnostic marker of disease. In contrast, CHI1 released by activated Kupffer cells in liver could induce hepatic fibrosis and cirrhosis. Increased serum levels of CHIT1 were observed in patients with many disorders, including Gaucher's disease, bronchial asthma, and atherosclerosis. Therefore, CHIT1 seems to have dual (regulatory and pathogenic) roles depending on the disease and producing cell types during the inflammatory conditions.

几丁质酶1在正常和疾病条件下的作用。
基于结构同源性,哺乳动物几丁质酶属于糖基水解酶18家族,该家族包括大量的细菌和真核生物几丁质酶。在哺乳动物几丁质酶中,chitotriosidase (CHIT1)和酸性哺乳动物几丁质酶(AMCase)能够水解几丁质相邻n -乙酰氨基葡萄糖残基之间的β-(1,4)-键。CHIT1是分泌最丰富的蛋白之一,主要由活化的巨噬细胞和上皮细胞产生。CHIT1在包括疟疾和真菌感染在内的传染病中发挥关键作用,作为宿主防御病原体细胞结构中的几丁质和作为疾病的诊断标志物。而激活的Kupffer细胞释放的CHI1可诱导肝纤维化和肝硬化。许多疾病患者血清中CHIT1水平升高,包括戈谢病、支气管哮喘和动脉粥样硬化。因此,CHIT1似乎具有双重(调节和致病)作用,这取决于疾病和炎症条件下产生的细胞类型。
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