Iron content of ferritin modulates its uptake by intestinal epithelium: implications for co-transport of prions.
Iron content of ferritin modulates its uptake by intestinal epithelium: implications for co-transport of prions.
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DOI：
10.1186/1756-6606-3-14
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发表时间：
2010-04-29
期刊：
影响因子：
3.6
通讯作者：
Singh N
中科院分区：
文献类型：
--
作者：
Bhupanapadu Sunkesula SR;Luo X;Das D;Singh A;Singh N
慢性消耗性疾病（CWD）在鹿和麋鹿种群中的传播由于其可能感染农场动物和人类而引起了严重的公共卫生问题。像其他朊病毒疾病，如人类的散发性克雅氏病和牛的疯牛病一样，CWD是由PrP-scrapie （PrPSc）引起的，PrPSc是正常细胞表面糖蛋白PrPC的一种富含β-sheet的异构体。由于PrPSc如果被易感宿主摄入，足以引起感染和神经毒性，因此了解其穿过小肠严格的上皮细胞屏障的机制非常重要。可能的机制包括与铁蛋白在摄入的食物中共同运输和被树突状细胞摄取。由于铁蛋白在物种中普遍表达，且具有相当大的同源性，PrPSc与铁蛋白的共转运可导致跨物种传播，并带来有害后果。我们使用了体外和体内肠道上皮细胞屏障模型来了解铁蛋白在介导PrPSc摄取和运输中的作用。在本报告中，我们证明了来自CWD的PrPSc和铁蛋白影响鹿和麋鹿的大脑，以及羊的痒病，抵抗消化酶的降解，并以显著的效率在人上皮细胞的紧密单层上进行转胞。同样，来自仓鼠大脑的铁蛋白在体内也会被小鼠肠上皮细胞吸收，这表明铁蛋白的吸收并不像朊病毒那样受到物种差异的限制。更重要的是，铁蛋白的铁含量决定了Caco-2细胞和小鼠模型对铁蛋白的摄取和运输效率，为肠上皮细胞对铁蛋白和PrPSc的摄取机制提供了新的思路。
The spread of Chronic Wasting Disease (CWD) in the deer and elk population has caused serious public health concerns due to its potential to infect farm animals and humans. Like other prion disorders such a sporadic Creutzfeldt-Jakob-disease of humans and Mad Cow Disease of cattle, CWD is caused by PrP-scrapie (PrPSc), a β-sheet rich isoform of a normal cell surface glycoprotein, the prion protein (PrPC). Since PrPSc is sufficient to cause infection and neurotoxicity if ingested by a susceptible host, it is important to understand the mechanism by which it crosses the stringent epithelial cell barrier of the small intestine. Possible mechanisms include co-transport with ferritin in ingested food and uptake by dendritic cells. Since ferritin is ubiquitously expressed and shares considerable homology among species, co-transport of PrPSc with ferritin can result in cross-species spread with deleterious consequences. We have used a combination of in vitro and in vivo models of intestinal epithelial cell barrier to understand the role of ferritin in mediating PrPSc uptake and transport. In this report, we demonstrate that PrPSc and ferritin from CWD affected deer and elk brains and scrapie from sheep resist degradation by digestive enzymes, and are transcytosed across a tight monolayer of human epithelial cells with significant efficiency. Likewise, ferritin from hamster brains is taken up by mouse intestinal epithelial cells in vivo, indicating that uptake of ferritin is not limited by species differences as described for prions. More importantly, the iron content of ferritin determines its efficiency of uptake and transport by Caco-2 cells and mouse models, providing insight into the mechanism(s) of ferritin and PrPSc uptake by intestinal epithelial cells.
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影响因子：
3.1
作者：
Gu, Yaping;Verghese, Susarnma;Singh, Neena
通讯作者：
Singh, Neena
影响因子：
3.3
作者：
Basu, Subhabrata;Mohan, Maradumane L.;Singh, Neena
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Singh, Neena
影响因子：
4.8
作者：
Gu, YP;Fujioka, H;Singh, N
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影响因子：
5.6
作者：
Kalgaonkar, Swati;Loennerdal, Bo
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Loennerdal, Bo
影响因子：
4.8
作者：
Jin, TC;Gu, YP;Singh, N
通讯作者：
Singh, N