Efficient degradation of gluten by a prolyl endoprotease in a gastrointestinal model: implications for coeliac disease
Efficient degradation of gluten by a prolyl endoprotease in a gastrointestinal model: implications for coeliac disease
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DOI：
10.1136/gut.2006.111609
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发表时间：
2008-01-01
期刊：
影响因子：
24.5
通讯作者：
Koning, F.
中科院分区：
文献类型：
--
作者：
Mitea, C.;Havenaar, R.;Koning, F.
背景：乳糜泻是由对谷蛋白的免疫反应引起的。由于麸质蛋白富含脯氨酸，它们在胃肠道中抵抗酶消化，这一特性可能有助于麸质的免疫原性。目的：本研究确定了一种脯氨酸后切割酶——黑曲霉脯氨酸内源性蛋白酶（AN-PEP）在一个模拟人类胃肠道（TIM系统）的动态系统中降解谷蛋白的效率。方法：进行两项实验。首先，在有或没有AN-PEP的情况下，在TIM系统中处理一片面包。在第二个实验中，使用的是标准的快餐菜单。试验开始后4小时，分别从胃、十二指肠、空肠和回肠各部采集消化物样品。在这些样品中，通过基于单克隆抗体的竞争分析、Western blot分析和增殖t细胞分析来评估麦胶蛋白和谷蛋白的免疫原性肽水平。结果：an - pep加速了谷蛋白在胃室的降解，以至于几乎没有谷蛋白到达十二指肠室。结论：AN-PEP能够在近似体内消化的胃肠道系统中加速谷蛋白的降解。这意味着AN-PEP与含谷蛋白的膳食共同施用可能消除谷蛋白毒性，从而为患者提供放弃（偶尔）严格的无谷蛋白饮食的可能性。
Background: Coeliac disease is caused by an immune response to gluten. As gluten proteins are proline rich they are resistant to enzymatic digestion in the gastrointestinal tract, a property that probably contributes to the immunogenic nature of gluten.Aims: This study determined the efficiency of gluten degradation by a post-proline cutting enzyme, Aspergillus niger prolyl endoprotease (AN-PEP), in a dynamic system that closely mimics the human gastrointestinal tract (TIM system).Methods: Two experiments were performed. In the first, a slice of bread was processed in the TIM system with and without co-administration of AN-PEP. In the second, a standard fast food menu was used. Samples of the digesting meals were taken from the stomach, duodenum, jejunum and ileum compartments at time zero until 4 hours after the start of the experiment. In these samples the levels of immunogenic peptides from gliadins and glutenins were assessed by monoclonal antibody-based competition assays, Western blot analysis and proliferation T-cell assays.Results: AN-PEP accelerated the degradation of gluten in the stomach compartment to such an extent that hardly any gluten reached the duodenum compartment.Conclusion: AN-PEP is capable of accelerating the degradation of gluten in a gastrointestinal system that closely mimics in-vivo digestion. This implies that the co-administration of AN-PEP with a gluten-containing meal might eliminate gluten toxicity, thus offering patients the possibility of abandoning (occasionally) their strict gluten-free diet.