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Mechanism of Prion Protein Absorption from Digestive Tract in Calves

犊牛消化道朊病毒蛋白吸收机制

基本信息

批准号：
15380189
负责人：
OBARA Yoshiaki
金额：
$ 10.24万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15380189/
关键词：
Bovine Spongiform Encephalophasy (BSE)Abnormal prion protein Horseradish peroxidase (HRP)Development of digestive tract Small intestine M cell the method with eventual sacks Ussing chamber method Hourseradish Peroxidase (HRP)ホルスタイン子ウシ

项目摘要

Although it has been suggested that abnormal Prion proteins are absorbed from the intestinal mucosa and infect many animal species with bovine spongiform encephalopathy (BSE), the detailed mechanisms remain clarified. The aim of the present study was to investigate Horseradish peroxidase (HRP) absorption, in which HRP was used instead of abnormal Prion proteins, and its mechanism in isolated segments of the duodenum, jejunum, ileum and colon from rabbits, sheep and Holstein calves by the methods with everted sacks and the Ussing chamber. We also observed morphological features of M cells in Peyer's patches by the immunochemical method and SEM.1)In calves, the HRP absorption was greater in the duodenum, jejunum and ileum than in the colon, and also was greater at the age of 13 weeks than at 4 weeks.2)In rabbits, the HRP absorption showed a tendency to be greater in the ileum than in the colon, and was dependent on aging, the intestine, H^+ gradient and Na^+/K^+-ATPase activities.3)In calves, the HRP absorption in the jejunum and ileum was greater at the age of 6 weeks than of 15 weeks, and was significantly decreased by the reduction of the medium pH from 7.4 to 5.4. It was also significantly increased by an addition of amiloride but not by ouabain.4)In the calf jejunal epithelium, it was indicated that M cells increase the cell number and promote the differentiation as the ruminal function develops, and accelerate the ability for absorption of higher molecules.These findings strongly suggest the possibility that the absorption of abnormal Prion proteins occur at the small intestine, mainly the ileum, after weaning.

虽然已有研究表明，异常的Prion蛋白可从肠道粘膜吸收，并感染多种动物的牛海绵状脑病(BSE)，但其具体机制仍不清楚。本研究的目的是用外翻袋和Ussing小室的方法研究辣根过氧化物酶(HRP)在兔、绵羊和荷斯坦小牛的十二指肠、空肠、回肠和结肠中的吸收及其机制。用免疫组织化学方法观察了小牛Peyer氏结M细胞的形态特征：1)小牛十二指肠、空肠和回肠对HRP的吸收大于结肠，13周龄大于4周龄；2)兔回肠对HRP的吸收有大于结肠的趋势，并与年龄、肠道、H~(++)梯度和Na~+/K~+-ATPase活性有关。当介质pH从7.4降至5.4时，产酶活性显著降低。在犊牛空肠上皮细胞中，随着瘤胃功能的发展，M细胞的数量增加，促进分化，促进对更高分子的吸收能力。这些发现有力地表明，断奶后异常的Prion蛋白的吸收发生在小肠，主要是回肠。