Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2009-11-13
pubmed:abstractText
Iron is used to cure iron-deficient anaemia but can also be toxic to the intestine. Fe(II) toxicity was investigated using differentiated human intestinal Caco-2 cells treated with 15 and 50 microM of Fe(II)/ascorbate for 2h (acute phase), and followed for 24h after iron removal and replacement of complete culture medium (late phase). During the acute phase damage to tight junctions occurred as demonstrated by an increase in cell monolayer permeability and by partial delocalization of the tight junction protein claudin 4 from the plasma membrane to an intracellular compartment. At the end of the late phase, cells treated with 15 microM Fe(II) showed full restoration of claudin 4 localization to the plasma membrane and their tight junction permeability returned to values close to those of control cells. Conversely, cells treated with 50 microM Fe(II) showed sustained and irreversible damage to the tight junctions, accompanied by apoptosis and necrosis. Activation of NF-kappaB occurred at both Fe(II) concentrations after 30 min of Fe(II) treatment, followed, at the end of the acute phase, by a strong induction of mRNA coding for heat shock protein 70 and metallothionein 2A. Our results indicate that intestinal cells respond to iron toxicity by strongly activating two genes involved in cell response to stress, although the outcome in terms of cell survival is different depending on the dose of treatment, namely almost complete restoration of epithelial permeability and cell survival at 15 microM Fe(II), and progressive and irreversible cytotoxicity leading to apoptosis and necrosis at 50 microM Fe(II).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1879-3177
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1510-5
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Mechanisms of defence from Fe(II) toxicity in human intestinal Caco-2 cells.
pubmed:affiliation
CNR, Institute of Neurobiology and Molecular Medicine, Via del Fosso di Fiorano 64, 00143 Rome, Italy. manuela.natoli@inmm.cnr.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't