PMID- 12605408
OWN - NLM
STAT- MEDLINE
DCOM- 20030507
LR  - 20151119
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 71
IP  - 6
DP  - 2003 Mar 15
TI  - Differential regulation of 5' splice variants of the glutamate transporter EAAT2 
      in an in vivo model of chemical hypoxia induced by 3-nitropropionic acid.
PG  - 819-25
AB  - Defective glutamate uptake has been implicated as a pathogenic event of neuronal 
      damage related to cerebral ischemia and hypoxia. In several models of 
      ischemia-hypoxia, a reduced immunoreactivity and altered RNA expression of 
      excitatory amino acid transporter 2 (EAAT2), the major excitatory amino acid 
      transporter, have been reported. However, the gene regulation of EAAT2 under 
      these conditions is incompletely understood. In this study, we investigated 
      alternative splicing of EAAT2 in an in vivo mouse model of chemical hypoxia as 
      induced by 3-nitropropionic acid (3-NP). The neurotoxin 3-NP is an inhibitor of 
      mitochondrial energy production. Furthermore, it is known to inhibit glutamate 
      reuptake directly, representing at least one of the mechanisms responsible for 
      3-NP-induced neurodegeneration. Here we report an expression analysis of five 
      known (mEAAT2/5UT1-5) and two novel (mEAAT2/5UT6, -7) 5' splice variants of EAAT2 
      using semiquantitative PCR. The RNA expression was studied at 2, 12, 24, 48, and 
      72 hr and 7 days after 3-NP administration. mEAAT2/5UT4 and mEAAT2/5UT5 were 
      up-regulated in the frontal cortex and down-regulated in the hippocampus 12-72 hr 
      after chemical hypoxia. In the cerebellum, there was an increased expression of 
      mEAAT2/5UT4 and a down-regulation of mEAAT2/5UT5. mEAAT2/5UT3 show a different 
      regional expression pattern, being regulated in the cerebellum only. 
      mEAAT2/5UT1-7 encoded distinct 5' regulatory sequences, including conserved 
      elements of translational control. It is easily conceivable that expression 
      alterations of 5' splice variants of EAAT2 are related to glutamate transporter 
      malfunction after chemical hypoxia. Our findings contribute to the hypothesis 
      that RNA splicing events can serve as a molecular mechanism of posthypoxic gene 
      regulation.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Munch, Christoph
AU  - Munch C
AD  - Department of Neurology, University of Ulm, Ulm, Germany.
FAU - Zhu, Bing-Gen
AU  - Zhu BG
FAU - Leven, Annette
AU  - Leven A
FAU - Stamm, Stefan
AU  - Stamm S
FAU - Einkorn, Hermann
AU  - Einkorn H
FAU - Schwalenstocker, Birgit
AU  - Schwalenstocker B
FAU - Ludolph, Albert C
AU  - Ludolph AC
FAU - Riepe, Matthias W
AU  - Riepe MW
FAU - Meyer, Thomas
AU  - Meyer T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Convulsants)
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (Nitro Compounds)
RN  - 0 (Propionates)
RN  - 0 (RNA, Messenger)
RN  - QY4L0FOX0D (3-nitropropionic acid)
SB  - IM
MH  - Alternative Splicing/*genetics
MH  - Animals
MH  - Brain/*physiology
MH  - Cloning, Molecular
MH  - Convulsants/pharmacology
MH  - Excitatory Amino Acid Transporter 2/genetics/*metabolism
MH  - *Gene Expression Regulation
MH  - Hypoxia, Brain/chemically induced/genetics/*metabolism
MH  - Male
MH  - Mice
MH  - Nitro Compounds
MH  - Polymerase Chain Reaction
MH  - Propionates/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Recombination, Genetic
EDAT- 2003/02/28 04:00
MHDA- 2003/05/08 05:00
CRDT- 2003/02/28 04:00
PHST- 2003/02/28 04:00 [pubmed]
PHST- 2003/05/08 05:00 [medline]
PHST- 2003/02/28 04:00 [entrez]
AID - 10.1002/jnr.10536 [doi]
PST - ppublish
SO  - J Neurosci Res. 2003 Mar 15;71(6):819-25. doi: 10.1002/jnr.10536.