Down-regulation of Cl- pump ClP55 subunit induced enhancement of glutamate neurotoxicity in cultured rat hippocampal neurons.
To test whether the increased intracellular Cl- concentration ([Cl-]i) is responsible for the enhanced glutamate toxicity, antisense oligonucleotide of ClP55, a Cl- -ATPase/pump associated protein, was transfected in cultured rat hippocampal neurons. Neuronal [Cl-]i in the antisense oligonucleotide-transfected culture increased to a level 3- to 4-fold higher than that in control. Glutamate exposure (10 microM, 10 min) increased neuronal apoptosis and decreased Akt-pS473 level in the antisense oligonucleotide-transfected neurons, but not in control or sense oligonucleotide-transfected ones, suggesting the responsibility of elevated [Cl-]i in the enhancement of glutamate neurotoxicity.
Li
Tiesong
T
Department of Pharmacology, Kansai Medical University, Fumizono-cho 10-15, Moriguchi, Osaka 570-8506, Japan.
Nakayama
Yasuhisa
Y
Kitagawa
Kaori
K
Hattori
Naoki
N
Xiong
Zheng-Mei
ZM
Inagaki
Chiyoko
C
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D027321:Anion Transport Proteins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D013437:Carbon-Sulfur Lyases / Q000378:metabolism; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D015536:Down-Regulation; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D016623:Ion Pumps / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D009498:Neurotoxins / Q000633:toxicity; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D021122:Protein Subunits; D051381:Rats; D017208:Rats, Wistar
D027321:Anion Transport Proteins; D002712:Chlorides; D016623:Ion Pumps; D009498:Neurotoxins; D016376:Oligonucleotides, Antisense; D021122:Protein Subunits; D018698:Glutamic Acid; D000251:Adenosine Triphosphatases; C031652:anion-sensitive ATPases; D013437:Carbon-Sulfur Lyases