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Impairment of glutamate transport and increased vulnerability to oxidative stress in neuroblastoma SH-SY5Y cells expressing a Cu,Zn superoxide dismutase typical of familial amyotrophic lateral sclerosis
- Source :
- Neurochemistry International. 46:227-234
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
Abstract
- Human neuroblastoma SH-SY5Y cells transfected with either familial amyotrophic lateral sclerosis-typical G93A mutant or wild-type copper/zinc superoxide dismutase were compared to untransfected cells in term of glutamate transport. V,,,, of glutamate uptake was reduced in mutant cells, with no change in Km. No difference in EAAT1, EAAT2 and EAAT3 glutamate transporter mRNAs and immunoreactive proteins was found, suggesting that one or more transporters are functionally inactivated, possibly due to increased oxidative stress induced by the G93A mutation. Mutant cells showed a marked sensitivity to oxidants, resulting in a more pronounced reduction of glutamate uptake. Short-term antioxidant treatment did not reverse the impairment of glutamate uptake in G93A cells. Interestlingly, N-acetylcysteine was partially effective in preventing glutamate uptake reduction due to exogenous oxidative insults. Since the inhibition of the EAAT2 transporter subtype had no effect on glutamate re-uptake in this model, our study suggests an impaired function of the EAAT1/3 transporter subtypes, possibly due to oxidative inactivation, in the presence of mutant copper/zinc superoxide dismutase. Therefore, this model might prove to be a valuable tool to study the effects of mutant copper/zinc superoxide dismutase associated with amyotrophic lateral sclerosis on glutamate transport in neuronal cells, without the specific contribution of glial cells. These findings might lead to the identification of new therapeutic strategies aimed at preventing the damage associated with ALS. (C) 2004 Elsevier Ltd. All rights reserved.
- Subjects :
- SH-SY5Y
Amino Acid Transport System X-AG
Messenger
Mutant
Excitotoxicity
medicine.disease_cause
Neuroblastoma
Agar Gel
glutamate uptake
amyotrophic lateral sclerosi
Superoxide Dismutase
Antioxidants
Glutamic Acid
Humans
Excitatory Amino Acid Transporter 3
Cell Line, Tumor
Reverse Transcriptase Polymerase Chain Reaction
Biological Transport, Active
Symporters
Sodium
RNA, Messenger
Brain Neoplasms
Excitatory Amino Acid Transporter 1
Amyotrophic Lateral Sclerosis
Kinetics
Oxidative Stress
Electrophoresis, Agar Gel
Mutation
Oxidants
Glutamate Plasma Membrane Transport Proteins
Tumor
biology
Glutamate receptor
Transfection
copper/zinc superoxide dismutase
antioxidants
Excitatory Amino Acid Transporter 2
Biochemistry
excitotoxicity
Electrophoresis
Active
Oxidative phosphorylation
Cell Line
Superoxide dismutase
Cellular and Molecular Neuroscience
medicine
Settore BIO/10
MED/26 - NEUROLOGIA
oxidative stre
Biological Transport
Cell Biology
Molecular biology
biology.protein
RNA
Oxidative stress
Subjects
Details
- ISSN :
- 01970186
- Volume :
- 46
- Database :
- OpenAIRE
- Journal :
- Neurochemistry International
- Accession number :
- edsair.doi.dedup.....0ee0b804fdc687f804ce6c400c979834