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PMID: 12578975 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Insights into glutamate transport regulation in human astrocytes: cloning of the promoter for excitatory amino acid transporter 2 (EAAT2).

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 4 ·2003-02-18 ·Pages 1955-60

Su ZZ, Leszczyniecka M, Kang DC, Sarkar D, Chao W, Volsky DJ, Fisher PB

Abstract

Glutamate transport is central to neurotransmitter functions in the brain. Impaired glutamate transport induces neurotoxicity associated with numerous pathological processes, including stroke/ischemia, temporal lobe epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, HIV-1-associated dementia, and growth of malignant gliomas. Excitatory amino acid transporter-2 (EAAT2) is a major glutamate transporter in the brain expressed primarily in astrocytes. We presently describe the cloning and characterization of the human EAAT2 promoter, demonstrating elevated expression in astrocytes. Regulators of EAAT2 transport, both positive and negative, alter EAAT2 transcription, promoter activity, mRNA, and protein. These findings imply that transcriptional processes can regulate EAAT2 expression. Moreover, they raise the intriguing possibility that the EAAT2 promoter may be useful for targeting gene expression in the brain and for identifying molecules capable of modulating glutamate transport that could potentially inhibit, ameliorate, or prevent various neurodegenerative diseases.

MeSH Terms
Astrocytes/metabolism Base Sequence Biological Transport Cells, Cultured Cloning, Molecular DNA Primers Excitatory Amino Acid Transporter 2/genetics Glutamic Acid/metabolism Humans Molecular Sequence Data Promoter Regions, Genetic RNA, Messenger/genetics,metabolism Transcription, Genetic
Chemicals
DNA Primers Excitatory Amino Acid Transporter 2 RNA, Messenger Glutamic Acid
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Su Zao-zhong
Department of Pathology, Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Leszczyniecka Magdalena
Kang Dong-chul
Sarkar Devanand
Chao Wei
Volsky David J
Fisher Paul B
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0136555100
Published
2003-02-18
Epub
2003-00-10
Pages
1955-60
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC149940
Subset
IM
Grants
NINDS NIH HHS · P01 NS031492 · United States
NINDS NIH HHS · NS31492 · United States
Databases
GENBANK
AF510107
External Links
PubMed source DOI: 10.1073/pnas.0136555100 PMC Full Text View journal details
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