Linked Life Data

12387356

Source:http://linkedlifedata.com/resource/pubmed/id/12387356

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-10-21
pubmed:abstractText
Manganese (Mn)-induced neurotoxicity can occur due to environmental exposure (air pollution, soil, water) and/or metabolic aberrations (decreased biliary excretion). High brain manganese levels lead to oxidative stress, as well as alterations in neurotransmitter metabolism with concurrent neurobehavioral deficits. Based on the few existing studies that have examined brain regional Mn concentration, it is likely that in pathological conditions, Mn concentration can reach between 100 and 500 microM. Environmental Mn exposure as a result of methylcyclopentadienyl manganese tricarbonyl (MMT) combustion is in the form of phosphate or sulfate (MnPO4, MnSO4, respectively). Pharmacokinetic studies have shown that the Mn salt will determine the rate of transport into the brain: MnCl2 > MnSO4 > MnPO4. The salt-specific neurotoxicity of these species is unknown. The primary goal of this study was to examine gene expression of glutamate/aspartate transporter (GLAST), taurine transporter (tau-T), and metallothionein-I (MT-I) in astrocytes exposed to manganese chloride (MnCl2), manganese sulfate (MnSO4), and manganese phosphate (MnPO4). We hypothesized that the effects of MnPO4 and MnSO4 exposure on GLASTexpression in astrocytes would be similar to those induced by MnCl2, since irrespective of salt species exposure, once internalized by astrocytes, the Mn ion would be identically complexed. At the same time, we hypothesized that the magnitude of the effect would be salt-dependent, since the chemical speciation would determine the rate of intracellular uptake of Mn. MnCl2 caused a significant overall decrease (P < 0.0001) in astrocytic GLAST mRNA levels with MnSO4 causing a moderate decrease. MnPO4 exposure did not alter GLAST mRNA in astrocytes. We also sought to examine astrocytic metallothionein and taurine transporter gene expression as markers of manganese exposure. Our findings suggest that manganese chloride significantly decreased (P < 0.0001) astrocytic metallothionein mRNA compared to both the sulfate and phosphate species. However, astrocytic taurine transporter mRNA was not affected by Mn exposure, irrespective of the salt species. These data are consistent with the hypothesis that astrocytic neurotoxicity due to Mn exposure is dependent upon its species, with solubility, and by inference, intracellular concentration, representing a major determinant of its neurotoxicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acid Transport System X-AG, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Chlorides, http://linkedlifedata.com/resource/pubmed/chemical/Manganese Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Metallothionein, http://linkedlifedata.com/resource/pubmed/chemical/Organometallic Compounds, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Sulfates, http://linkedlifedata.com/resource/pubmed/chemical/manganese chloride, http://linkedlifedata.com/resource/pubmed/chemical/manganese phosphate, http://linkedlifedata.com/resource/pubmed/chemical/manganese sulfate, http://linkedlifedata.com/resource/pubmed/chemical/taurine transporter
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0161-813X
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
281-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Glutamate/aspartate transporter (GLAST), taurine transporter and metallothionein mRNA levels are differentially altered in astrocytes exposed to manganese chloride, manganese phosphate or manganese sulfate.
pubmed:affiliation
Department of Physiology and Pharmacology, School of Medicine, Wake Forest University, Winston-Salem 27157-1083, USA. kerikson@wfubmc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't