Linked Life Data

15009675

Source:http://linkedlifedata.com/resource/pubmed/id/15009675

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-3-10
pubmed:abstractText
The cellular uptake and storage of iron have to be tightly regulated in order to provide iron for essential cellular functions while preventing the iron-catalysed generation of reactive oxygen species (ROS). In contrast to cells in other organs, little is known about the regulation of iron metabolism in brain cells, particularly in astrocytes. To investigate the regulation of iron metabolism in astrocytes we have used primary astrocyte cultures from the brains of newborn rats. After application of ferric ammonium citrate (FAC), cultured astrocytes accumulated iron in a time- (0-48 h) and concentration-dependent (0.01-1 mm) manner. This accumulation was prevented if FAC was applied in combination with the iron-chelator deferoxamine (DFX). Application of FAC to astrocyte cultures caused a strong increase in the cellular content of the iron storage protein ferritin and a decrease in the amount of transferrin receptor (TfR), which is involved in the transferrin-mediated uptake of iron into cells. In contrast, application of DFX strongly increased the level of TfR. Both up-regulation of ferritin content by iron application and up-regulation of TfR content by DFX were prevented by the protein synthesis inhibitor cycloheximide (CHX). During incubation of astrocytes with FAC, a mild and transient increase in the extracellular activity of the cytosolic enzyme lactate dehydrogenase and in the concentration of intracellular ROS was observed. In contrast, prevention of protein synthesis by CHX during incubation with FAC resulted in significantly more cell loss and a persistent and intense increase in the production of intracellular ROS. These results demonstrate that both iron accumulation and deprivation modulate the synthesis of ferritin and TfR in astrocytes and that protein synthesis is required to prevent iron-mediated toxicity in astrocytes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1194-202
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Iron accumulation, iron-mediated toxicity and altered levels of ferritin and transferrin receptor in cultured astrocytes during incubation with ferric ammonium citrate.
pubmed:affiliation
Physiolologisch-chemisches Institut der Universität, Tübingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't