QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, December 15, 2004, 24(50):11280-11290; doi:10.1523/JNEUROSCI.2864-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (25) Citing Articles via Google Scholar Google Scholar Articles by Mishra, R. S. Articles by Singh, N. Search for Related Content PubMed PubMed Citation Articles by Mishra, R. S. Articles by Singh, N.

 Previous Article  |  Next Article 

Neurobiology of Disease
Protease-Resistant Human Prion Protein and Ferritin Are Cotransported across Caco-2 Epithelial Cells: Implications for Species Barrier in Prion Uptake from the Intestine

Ravi Shankar Mishra, ^* Subhabrata Basu, ^* Yaping Gu, Xiu Luo, Wen-Quan Zou, Richa Mishra, Ruliang Li, Shu G. Chen, Pierluigi Gambetti, Hisashi Fujioka, and Neena Singh

Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106

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.

Key words: prion infection; subclinical infection; PrP transport; new variant CJD; ferritin; epithelial cell barrier; Caco-2

---

Received July 15, 2004; revised October 27, 2004; accepted November 2, 2004.

This article has been cited by other articles:

				C. R. Raymond, P. Aucouturier, and N. A. Mabbott In Vivo Depletion of CD11c+ Cells Impairs Scrapie Agent Neuroinvasion from the Intestine J. Immunol., December 1, 2007; 179(11): 7758 - 7766. [Abstract] [Full Text] [PDF]

				S. Paquet, N. Daude, M.-P. Courageot, J. Chapuis, H. Laude, and D. Vilette PrPc Does Not Mediate Internalization of PrPSc but Is Required at an Early Stage for De Novo Prion Infection of Rov Cells J. Virol., October 1, 2007; 81(19): 10786 - 10791. [Abstract] [Full Text] [PDF]

				S. Basu, M. L. Mohan, X. Luo, B. Kundu, Q. Kong, and N. Singh Modulation of Proteinase K-resistant Prion Protein in Cells and Infectious Brain Homogenate by Redox Iron: Implications for Prion Replication and Disease Pathogenesis Mol. Biol. Cell, September 1, 2007; 18(9): 3302 - 3312. [Abstract] [Full Text] [PDF]

				J. Fisher, K. Devraj, J. Ingram, B. Slagle-Webb, A. B. Madhankumar, X. Liu, M. Klinger, I. A. Simpson, and J. R. Connor Ferritin: a novel mechanism for delivery of iron to the brain and other organs Am J Physiol Cell Physiol, August 1, 2007; 293(2): C641 - C649. [Abstract] [Full Text] [PDF]

				D. S. Spinner, R. B. Kascsak, G. LaFauci, H. C. Meeker, X. Ye, M. J. Flory, J. I. Kim, G. B. Schuller-Levis, W. R. Levis, T. Wisniewski, et al. CpG oligodeoxynucleotide-enhanced humoral immune response and production of antibodies to prion protein PrPSc in mice immunized with 139A scrapie-associated fibrils J. Leukoc. Biol., June 1, 2007; 81(6): 1374 - 1385. [Abstract] [Full Text] [PDF]

				R E Duncan, M B Delatycki, S J Collins, A Boyd, C L Masters, and J Savulescu Ethical considerations in presymptomatic testing for variant CJD J. Med. Ethics, November 1, 2005; 31(11): 625 - 630. [Abstract] [Full Text] [PDF]

				J. Novakofski, M. S. Brewer, N. Mateus-Pinilla, J. Killefer, and R. H. McCusker Prion biology relevant to bovine spongiform encephalopathy J Anim Sci, June 1, 2005; 83(6): 1455 - 1476. [Abstract] [Full Text] [PDF]

				A. C. Magalhaes, G. S. Baron, K. S. Lee, O. Steele-Mortimer, D. Dorward, M. A. M. Prado, and B. Caughey Uptake and Neuritic Transport of Scrapie Prion Protein Coincident with Infection of Neuronal Cells J. Neurosci., May 25, 2005; 25(21): 5207 - 5216. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help