Does human leukocyte elastase degrade intact skin elastin?
Does human leukocyte elastase degrade intact skin elastin?
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DOI：
10.1111/febs.12012
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发表时间：
2012-11-01
期刊：
影响因子：
5.4
通讯作者：
Heinz, Andrea
中科院分区：
文献类型：
--
作者：
Schmelzer, Christian E. H.;Jung, Michael C.;Heinz, Andrea
本研究旨在研究完整纤维状人类弹性蛋白对人类白细胞弹性蛋白酶和组织蛋白酶 G 的敏感性。弹性蛋白是脊椎动物细胞外基质的重要蛋白质，为许多组织和器官（包括主动脉、肺、软骨、弹性韧带和皮肤）提供弹性和拉伸强度等特殊特性，因此对其长期功能至关重要。成熟的弹性蛋白是一种不溶性且极其耐用的蛋白质，其周转率非常低，但持续暴露于蛋白酶可能会导致不可逆的严重损伤，从而导致弹性纤维网络的功能丧失。因此，了解哪些酶在某些病理条件下或内在衰老过程中实际上启动弹性分解是一个关键问题。在本文中，我们提供了一个完整的工作流程，用于从非常小的组织样本中分离纯净且完整的弹性蛋白，以测试酶的弹性分解潜力。该工作流程应用于不同年龄个体的皮肤样本，发现所研究的弹性蛋白的降解性存在很大差异。总之，人白细胞弹性蛋白酶不能降解完整的弹性蛋白纤维，但可以水解来自老年人皮肤的弹性蛋白。然而，组织蛋白酶 G 会裂解所有弹性蛋白样本，甚至包括来自年轻个体的弹性蛋白样本。这些结果表明，人白细胞弹性蛋白酶不是弹性分解的驱动力，但在组织蛋白酶 G 等其他酶的作用后可能会促进弹性纤维的进一步分解。
This study aimed to investigate the susceptibility of intact fibrillar human elastin to human leukocyte elastase and cathepsin G. Elastin is a vital protein of the extracellular matrix of vertebrates, and provides exceptional properties including elasticity and tensile strength to many tissues and organs, including the aorta, lung, cartilage, elastic ligaments and skin, and is thus critical for their long-term function. Mature elastin is an insoluble and extremely durable protein that undergoes very little turnover, but sustained exposure to proteases may lead to irreversible and severe damage, and thus to functional loss of the elastic fiber network. Hence, it is a key issue to understand which enzymes actually initiate elastolysis under certain pathological conditions or during intrinsic aging. In this paper, we provide a complete workflow for isolation of pure and intact elastin from very small tissue samples to test enzymes for their elastolytic potential. This workflow was applied to skin samples from variously aged individuals, and it was found that strong differences exist in the degradability of the elastins investigated. In summary, human leukocyte elastase was unable to degrade intact elastin fibers but hydrolyzed elastin derived from the skin of old people. However, cathepsin G cleaved all elastin samples, even those derived from younger individuals. These results indicate that human leukocyte elastase is not a driving force for elastolysis, but may nevertheless promote further breakdown of elastic fibers after the action of other enzymes such as cathepsin G.