Upregulation of the heteromeric y(+)LAT2 transporter contributes to ammonia-induced increase of arginine uptake in rat cerebral cortical astrocytes |
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Authors: | Zielińska Magdalena Skowrońska Marta Fr??ko Inez Albrecht Jan |
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Institution: | Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5 Str., 02-106 Warsaw, Poland. |
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Abstract: | Increased l-Arg (Arg) uptake to astrocytes and neurons is thought to contribute to enhanced nitric oxide (NO) synthesis and oxidative/nitrosative stress associated with hyperammonemia (HA). Recently we had shown that HA increases the expression in the brain of y(+)LAT2, an isoform of the y(+)L heteromeric transporter which promotes (3)H]Arg efflux form brain cells in the presence of l-glutamine (Gln) (Zielińska et al., 2011). In this study, we demonstrate that a significant proportion of (3)H]Arg uptake to cultured cortical astrocytes is likewise mediated by system y(+)L, in addition to the uptake showing characteristics of systems y(+), B(0+) and b(0+). However, stimulation of (3)H]Arg uptake by treatment with 5mM ammonium chloride ("ammonia") for 48h could be solely ascribed to the y(+)L-mediated component of the uptake. Ammonia treatment increased the expression of the brain specific y(+)L isoform, y(+)LAT2, both at the mRNA and protein level, and silencing of the Slc7a6 gene coding for y(+)LAT2 protein specifically reduced the ammonia-induced (3)H]Arg uptake. This study suggests an important role of y(+)LAT2 in the modulation of NO synthesis in the ammonia-exposed astrocytes. |
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Keywords: | NO nitric oxide NOS nitric oxide synthase Arg l-arginine Ala l-alanine Leu l-leucine HA hyperammonemia Gln l-glutamine CAT cationic amino acid transporter FBS fetal bovine serum KB Krebs Buffer GAPDH glyceraldehyde 3-phosphate dehydrogenase 4F2hc 4F2 heavy chain SLC solute carrier PCR polymerase chain reaction |
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