Insights into glutamate transport regulation in human astrocytes: cloning of the promoter for excitatory amino acid transporter 2 (EAAT2).
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.
Su
Zao-zhong
ZZ
Department of Pathology, Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Leszczyniecka
Magdalena
M
Kang
Dong-chul
DC
Sarkar
Devanand
D
Chao
Wei
W
Volsky
David J
DJ
Fisher
Paul B
PB
D001253:Astrocytes / Q000378:metabolism*; D001483:Base Sequence; D001692:Biological Transport; D002478:Cells, Cultured; D003001:Cloning, Molecular; D017931:DNA Primers; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D017931:DNA Primers; D027342:Excitatory Amino Acid Transporter 2; D012333:RNA, Messenger; D018698:Glutamic Acid