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From: TSS (216-119-143-96.ipset23.wt.net)
Subject: Re: New study shows how mad cow prions hitch a ride into intestine
Date: December 15, 2004 at 12:20 pm PST

In Reply to: New study shows how mad cow prions hitch a ride into intestine posted by Terry S. Singeltary Sr. on December 14, 2004 at 5:22 pm:

-------- Original Message --------
Subject: Protease-Resistant Human Prion Protein and Ferritin Are Cotransported across Caco-2 Epithelial Cells: Implications for Species Barrier in Prion Uptake from the Intestine
Date: Wed, 15 Dec 2004 14:11:24 -0600
From: "Terry S. Singeltary Sr."
To: Bovine Spongiform Encephalopathy
CC: cjdvoice@yahoogroups.com


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 (PrPSc), 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 PrPSc core of 27-30 kDa implicated in prion
disease transmission and pathogenesis. Notably, DE treatment results in
a PrPSc-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 PrPC expression.
Unexpectedly, PrPSc is cotransported with ferritin, a prominent
component of the DE-treated PrPSc-protein complex. The transport of
PrPSc-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 PrPSc-associated proteins, in particular ferritin, may facilitate
PrPSc 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.

http://www.jneurosci.org/cgi/content/abstract/24/50/11280

TSS





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