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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Protease-resistant human prion protein and ferritin are cotransported across Caco-2 epithelial cells: implications for species barrier in prion uptake from the intestine.
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Protease-resistant human prion protein and ferritin are cotransported across Caco-2 epithelial cells: implications for species barrier in prion uptake from the intestine.

机译：耐蛋白酶的人类病毒蛋白和铁蛋白共转运至Caco-2上皮细胞：影响肠道中barrier病毒摄取的物种屏障。

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摘要

Foodborne transmission of bovine spongiform encephalopathy (BSE) to humans as variant Creutzfeldt-Jakob disease (CJD) has affected over 100 individuals, and probably millions of others have been exposed to BSE-contaminated food substances. Despite these obvious public health concerns, surprisingly little is known about the mechanism by which PrP-scrapie (PrP(Sc)), the most reliable surrogate marker of infection in BSE-contaminated food, crosses the human intestinal epithelial cell barrier. Here we show that digestive enzyme (DE) treatment of sporadic CJD brain homogenate generates a C-terminal fragment similar to the proteinase K-resistant PrP(Sc) core of 27-30 kDa implicated in prion disease transmission and pathogenesis. Notably, DE treatment results in a PrP(Sc)-protein complex that is avidly transcytosed in vesicular structures across an in vitro model of the human intestinal epithelial cell barrier, regardless of the amount of endogenous PrP(C) expression. Unexpectedly, PrP(Sc) is cotransported with ferritin, a prominent component of the DE-treated PrP(Sc)-protein complex. The transport of PrP(Sc)-ferritin is sensitive to low temperature, brefeldin-A, and nocodazole treatment and is inhibited by excess free ferritin, implicating a receptor- or transporter-mediated pathway. Because ferritin shares considerable homology across species, these data suggest that PrP(Sc)-associated proteins, in particular ferritin, may facilitate PrP(Sc) uptake in the intestine from distant species, leading to a carrier state in humans.
机译：牛海绵状脑病（BSE）的食源性传播是Creutzfeldt-Jakob病（CJD）变种，已经影响了100多个个体，而且可能有数百万其他人接触了BSE污染的食物。尽管存在这些明显的公共卫生问题，但令人惊讶的是，对于被BSE污染食品中最可靠的替代感染标志物PrP-scrapie（PrP（Sc））穿过人肠上皮细胞屏障的机制知之甚少。在这里，我们显示零星CJD脑匀浆的消化酶（DE）处理产生的C末端片段类似于27-30 kDa的蛋白酶K抗性PrP（Sc）核心，与病毒疾病的传播和发病机理有关。值得注意的是，DE处理会导致PrP（Sc）-蛋白复合物在人肠上皮细胞屏障体外模型的囊泡结构中狂热地转胞吞，而与内源性PrP（C）表达的量无关。出乎意料的是，PrP（Sc）与铁蛋白共转运，铁蛋白是经DE处理的PrP（Sc）-蛋白质复合物的重要成分。 PrP（Sc）-铁蛋白的转运对低温，布雷菲德菌素A和诺考达唑治疗敏感，并被过量的游离铁蛋白抑制，这牵涉受体或转运蛋白介导的途径。由于铁蛋白在各个物种之间具有相当的同源性，因此这些数据表明，与PrP（Sc）相关的蛋白质，尤其是铁蛋白，可能会促进肠道中的PrP（Sc）从远处的物种中吸收，从而导致人类带菌。

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