Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P02794 (
ferritin
)
17,525
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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 beta-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.
...
PMID:Iron content of ferritin modulates its uptake by intestinal epithelium: implications for co-transport of prions. 2042 7
