Manganese causes differential regulation of glutamate transporter (GLAST) taurine transporter and metallothionein in cultured rat astrocytes.
Neurotoxicity due to excessive brain manganese (Mn) can occur due to environmental (air pollution, soil, water) and/ or metabolic aberrations (decreased biliary excretion). Manganese is associated with 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], it is likely that in pathological conditions it can reach 100-500 microM. Amino acid (e.g. aspartate, glutamate, taurine), as well as divalent metal (e.g. zinc, manganese) concentrations are regulated by astrocytes in the brain. Recently, it has been reported that cultured rat primary astrocytes exposed to Mn displayed decreased glutamate uptake, thereby, increasing the excitotoxic potential of glutamate. Since the neurotoxic mechanism(s) Mn employs in terms of glutamate metabolism is unknown, a primary goal of this study was to link altered glutamate uptake in Mn exposed astrocytes to alterations in glutamate transporter message. Further, we wanted to examine the gene expression of metallothionein (MT) and taurine transporter (tau-T) as markers of Mn exposure. Glutamate uptake was decreased by nearly 40% in accordance with a 48% decrease in glutamate/aspartate transporter (GLAST) mRNA. Taurine uptake was unaffected by Mn exposure even though tau-T mRNA increased by 123%. MT mRNA decreased in these Mn exposed astrocytes possibly due to altered metal metabolism, although this was not examined. These data show that glutamate and taurine transport in Mn exposed astrocytes are temporally different.
Erikson
Keith
K
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA. kerikson@wfubmc.edu
Aschner
Michael
M
D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D008345:Manganese / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008668:Metallothionein / Q000378:metabolism*; D051381:Rats; D013654:Taurine / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism; D000099247:Taurine Transporters
D027322:Amino Acid Transport System X-AG; D001224:Aspartic Acid; D002352:Carrier Proteins; D008345:Manganese; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008668:Metallothionein; D013654:Taurine; D016875:tau Proteins; D000099247:Taurine Transporters