Upregulation of the heteromeric y⁺LAT2 transporter contributes to ammonia-induced increase of arginine uptake in rat cerebral cortical astrocytes.
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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 48 h 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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| Authors | Magdalena Zielińska, Marta Skowrońska, Inez Fręśko, Jan Albrecht |
| Journal | Neurochemistry international (Neurochem Int) Vol. 61 Issue 4 Pg. 531-5 (Sep 2012) ISSN: 1872-9754 [Electronic] England |
| PMID | 22401943 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2012 Elsevier Ltd. All rights reserved. |
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