Linked Life Data

20819077

Source:http://linkedlifedata.com/resource/pubmed/id/20819077

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-10-25
pubmed:abstractText
Astrocytes are central to iron and ascorbate homoeostasis within the brain. Although NTBI (non-transferrin-bound iron) may be a major form of iron imported by astrocytes in vivo, the mechanisms responsible remain unclear. The present study examines NTBI uptake by cultured astrocytes and the involvement of ascorbate and DMT1 (divalent metal transporter 1). We demonstrate that iron accumulation by ascorbate-deficient astrocytes is insensitive to both membrane-impermeant Fe(II) chelators and to the addition of the ferroxidase caeruloplasmin. However, when astrocytes are ascorbate-replete, as occurs in vivo, their rate of iron accumulation is doubled. The acquisition of this additional iron depends on effluxed ascorbate and can be blocked by the DMT1 inhibitor ferristatin/NSC306711. Furthermore, the calcein-accessible component of intracellular labile iron, which appears during iron uptake, appears to consist of only Fe(III) in ascorbate-deficient astrocytes, whereas that of ascorbate-replete astrocytes comprises both valencies. Our data suggest that an Fe(III)-uptake pathway predominates when astrocytes are ascorbate-deficient, but that in ascorbate-replete astrocytes, at least half of the accumulated iron is initially reduced by effluxed ascorbate and then imported by DMT1. These results suggest that ascorbate is intimately involved in iron accumulation by astrocytes, and is thus an important contributor to iron homoeostasis in the mammalian brain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1470-8728
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
432
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
123-32
pubmed:dateRevised
2011-9-6
pubmed:meshHeading
pubmed-meshheading:20819077-Animals, pubmed-meshheading:20819077-Animals, Newborn, pubmed-meshheading:20819077-Antioxidants, pubmed-meshheading:20819077-Ascorbic Acid, pubmed-meshheading:20819077-Astrocytes, pubmed-meshheading:20819077-Biological Transport, pubmed-meshheading:20819077-Biphenyl Compounds, pubmed-meshheading:20819077-Cation Transport Proteins, pubmed-meshheading:20819077-Cells, Cultured, pubmed-meshheading:20819077-Dose-Response Relationship, Drug, pubmed-meshheading:20819077-Ferric Compounds, pubmed-meshheading:20819077-Ferrous Compounds, pubmed-meshheading:20819077-Hydrogen-Ion Concentration, pubmed-meshheading:20819077-Iron, pubmed-meshheading:20819077-Rats, pubmed-meshheading:20819077-Rats, Wistar, pubmed-meshheading:20819077-Sulfones, pubmed-meshheading:20819077-Time Factors
pubmed:year
2010
pubmed:articleTitle
Two routes of iron accumulation in astrocytes: ascorbate-dependent ferrous iron uptake via the divalent metal transporter (DMT1) plus an independent route for ferric iron.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't