title: Arsenite exposure downregulates EAAT1/GLAST transporter expression in glial cells.
abstract: Chronic exposure to inorganic arsenic severely damages the central nervous system (CNS). Glutamate (GLU) is the major excitatory amino acid and is highly neurotoxic when levels in the synaptic cleft are not properly regulated by a family of Na⁺-dependent excitatory amino acid transporters. Within the cerebellum, the activity of the Bergmann glia Na⁺-dependent GLU/aspartate transporter (GLAST) excitatory amino acid transporter 1 (EAAT1/GLAST) accounts for more than 90% of GLU uptake. Because exposure to the metalloid arsenite results in CNS toxicity, we examined whether EAAT1/GLAST constitutes a molecular target. To this end, primary cultures of chick cerebellar Bergmann glial cells were exposed to sodium arsenite for 24 h, and EAAT1/GLAST activity was evaluated via ³H-D-aspartate uptake. A sharp decrease in GLU transport was observed, and kinetic studies revealed protein kinase A, protein kinase C, and p38 mitogen-activated protein kinase-dependent decreases in K(M) and V(max) concomitant with diminished chglast transcription. To gain insight into the molecular mechanisms involved in these phenomena, we investigated the generation of reactive oxidative species and the lipid peroxidative damage caused by arsenite exposure. None of these responses were found, although we did observe an increase in nuclear factor (erythroid-derived 2)-like 2 DNA-binding activity correlated with a rise in total glutathione levels. Our results clearly suggest that EAAT1/GLAST is a molecular target of arsenite and support the critical involvement of glial cells in brain function and dysfunction.
authors: Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del IPN, México, D.F. México.
authors: Yaneth
authors: Y
authors: Castro-Coronel
authors: Luz María
authors: LM
authors: Del Razo
authors: Miriam
authors: M
authors: Huerta
authors: Angeles
authors: A
authors: Hernandez-Lopez
authors: Arturo
authors: A
authors: Ortega
authors: Esther
authors: E
authors: López-Bayghen