Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-8-21
pubmed:abstractText
Previous studies in this laboratory indicated that manganese (Mn) exposure in vitro increases the expression of transferrin receptor (TfR) by enhancing the binding of iron regulatory proteins (IRPs) to iron responsive element-containing RNA. The current study further tested the hypothesis that in vivo exposure to Mn increased TfR expression at both blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier (BCB), which contributes to altered iron (Fe) homeostasis in the CSF. Groups of rats (10-11 each) received oral gavages at doses of 5 mg Mn/kg or 15 mg Mn/kg as MnCl(2) once daily for 30 days. Blood, CSF, and choroid plexus were collected and brain capillary fractions were separated from the regional parenchyma. Metal analyses showed that oral Mn exposure decreased concentrations of Fe in serum (-66%) but increased Fe in the CSF (+167%). Gel shift assay showed that Mn caused a dose-dependent increase of binding of IRP1 to iron responsive element-containing RNA in BCB in the choroid plexus (+70%), in regional BBB of capillaries of striatum (+39%), hippocampus (+56%), frontal cortex (+49%), and in brain parenchyma of striatum (+67%), hippocampus (+39%) and cerebellum (+28%). Real-time RT-PCR demonstrated that Mn exposure significantly increased the expression of TfR mRNA in choroid plexus and striatum with concomitant reduction in the expression of ferritin (Ft) mRNA. Collectively, these data indicate that in vivo Mn exposure results in Fe redistribution in body fluids through regulating the expression of TfR and ferritin at BCB and selected regional BBB. The disrupted Fe transport by brain barriers may underlie the distorted Fe homeostasis in the CSF.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0161-813X
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
737-44
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16545456-Animals, pubmed-meshheading:16545456-Blood-Brain Barrier, pubmed-meshheading:16545456-Blotting, Northern, pubmed-meshheading:16545456-Brain, pubmed-meshheading:16545456-Brain Chemistry, pubmed-meshheading:16545456-Cerebrospinal Fluid, pubmed-meshheading:16545456-Dose-Response Relationship, Drug, pubmed-meshheading:16545456-Gene Expression Regulation, pubmed-meshheading:16545456-Iron, pubmed-meshheading:16545456-Male, pubmed-meshheading:16545456-Manganese, pubmed-meshheading:16545456-RNA, Messenger, pubmed-meshheading:16545456-Rats, pubmed-meshheading:16545456-Rats, Sprague-Dawley, pubmed-meshheading:16545456-Receptors, Transferrin, pubmed-meshheading:16545456-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16545456-Spectrophotometry, Atomic, pubmed-meshheading:16545456-Time Factors
pubmed:year
2006
pubmed:articleTitle
Molecular mechanism of distorted iron regulation in the blood-CSF barrier and regional blood-brain barrier following in vivo subchronic manganese exposure.
pubmed:affiliation
School of Health Sciences, Purdue University, 550 Stadium Mall Drive, CIVL 1163D, West Lafayette, IN 47907, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural