Accessibility navigation

Expression of SOD1 G93A or wild-type SOD1 in primary cultures of astrocytes down-regulates the glutamate transporter GLT-1: lack of involvement of oxidative stress

Tortarolo, M., Crossthwaite, A.J., Conforti, L., Spencer, J.P.E. ORCID:, Williams, R.J., Bendotti, C. and Rattray, M. (2004) Expression of SOD1 G93A or wild-type SOD1 in primary cultures of astrocytes down-regulates the glutamate transporter GLT-1: lack of involvement of oxidative stress. Journal of Neurochemistry, 88 (2). pp. 481-493. ISSN 0022-3042

Full text not archived in this repository.

It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing.

To link to this item DOI: 10.1046/j.1471-4159.2003.02208.x


Glutamate excitotoxicity is implicated in the aetiology of amyotrophic lateral sclerosis (ALS) with impairment of glutamate transport into astrocytes a possible cause of glutamate-induced injury to motor neurons. It is possible that mutations of Cu/Zn superoxide dismutase (SOD1), responsible for about 20% of familial ALS, down-regulates glutamate transporters via oxidative stress. We transfected primary mouse astrocytes to investigate the effect of the FALS-linked mutant hSOD1(G93A) and wild-type SOD1 (hSOD1(wt)) on the glutamate uptake system. Using western blotting, immunocytochemistry and RT-PCR it was shown that expression of either hSOD1(G93A) or hSOD1(wt) in astrocytes produced down-regulation of the levels of a glutamate transporter GLT-1, without alterations in its mRNA level. hSOD1(G93A) or hSOD1(wt) expression caused a decrease of the monomeric form of GLT-1 without increasing oxidative multimers of GLT-1. The effects were selective to GLT-1, since another glutamate transporter GLAST protein and mRNA levels were not altered. Reflecting the decrease in GLT-1 protein, [H-3]D-aspartate uptake was reduced in cultures expressing hSOD1(G93A) or hSOD1(wt). The hSOD1-induced decline in GLT-1 protein and [H-3]D-aspartate uptake was not blocked by the antioxidant Trolox nor potentiated by antioxidant depletion using catalase and glutathione peroxidase inhibitors. Measurement of 2',7'-dichlorofluorescein (DCF)-induced fluorescence revealed that expression of hSOD1(G93A) or hSOD1(wt) in astrocytes does not lead to detectable increase of intracellular reactive oxygen species. This study suggests that levels of GLT-1 protein in astrocytes are reduced rapidly by overexpression of hSOD1, and is due to a property shared between the wild-type and G93A mutant form, but does not involve the production of intracellular oxidative stress.

Item Type:Article
Divisions:Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences
ID Code:12948
Uncontrolled Keywords:excitatory amino acid transporter 1, excitatory amino acid transporter 2, glutamate aspartate transporter, glutamate transporter, motor neuron disease, superoxide dismutase , AMYOTROPHIC-LATERAL-SCLEROSIS, CU,ZN-SUPEROXIDE DISMUTASE MUTANT, CU,ZN SUPEROXIDE-DISMUTASE, HYDROGEN-PEROXIDE, HIGH-AFFINITY, SPINAL-CORD, TRANSGENIC MICE, K-M, MODEL, DEGENERATION

University Staff: Request a correction | Centaur Editors: Update this record

Page navigation