Denatured human α-defensin attenuates the bactericidal activity and the stability against enzymatic digestion
Denatured human α-defensin attenuates the bactericidal activity and the stability against enzymatic digestion
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DOI：
10.1016/j.bbrc.2007.04.132
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发表时间：
2007-06-22
影响因子：
3.1
通讯作者：
Kohgo, Yutaka
中科院分区：
文献类型：
--
作者：
Tanabe, Hiroki;Ayabe, Tokiyoshi;Kohgo, Yutaka
α-防御素是一种在天然免疫中起重要作用的抗菌肽。人防御素（HD）-5作为前体形式储存在小肠的潘氏细胞中，并被胰蛋白酶切割，胰蛋白酶从潘氏细胞颗粒共分泌。成熟的HD-5被保护免于被蛋白水解酶进一步消化。我们产生了重组HD-5和proHD-5以及每种肽的还原形式，以确定它们的二硫键的生理作用。还原的proHD-5减弱了杀菌活性和对胰蛋白酶消化的稳定性。二硫键保护人防御素免受酶降解。我们进一步纯化了克罗恩病患者小肠中具有二硫键变异的HD-5。HD-5对胰蛋白酶处理敏感。这些观察结果显然预示防御素缺乏可能是由疾病中的二硫键紊乱引起的。(c)2007年爱思唯尔公司All rights reserved.
alpha-Defensin is an antimicrobial peptide which plays an important role in innate immunity. Human defensin (HD)-5 is stored in the Paneth cells of the small intestine as a pro-form and is cleaved by trypsin, which is co-secreted from the Paneth cell granules. The mature HD-5 is protected from further digestion by the proteolysis enzyme, We generated both recombinant HD-5 and proHD-5, and the reduced form of each peptide in order to determine their physiological roles of the disulfide bonds. The reduced proHD-5 attenuated the bactericidal activity and the stability against the trypsin digestion. Human defensin was protected from the enzymatic degradation by disulfide bridges. We further purified the HD-5 with a disulfide variation in the small intestine of Crohn's disease patients. The HD-5 was sensitive to the trypsin treatment. These observations evidently predict that a defensin deficiency may be caused by a disulfide disorder in the disease. (c) 2007 Elsevier Inc. All rights reserved.