Amyloid beta protein enhances the clearance of extracellular L-glutamate by cultured rat cortical astrocytes.
To explore the impact of Alzheimer's disease amyloid beta protein (Abeta) on astrocyte functions, we investigated the effect of Abeta on glutamate clearance capacity of cultured rat cortical astrocytes. When L-glutamate (50-200 microM) was added to astrocyte cultures and incubated, the extracellular L-glutamate concentration declined with time. The time-dependent decline of extracellular L-glutamate was significantly faster in cultures treated with 10-20 microM Abeta for 24 h than in intact cultures, suggesting that Abeta enhances the L-glutamate clearance capacity of astrocytes. The effect of Abeta was not affected by antioxidants including catalase, propyl gallate or Trolox. Relatively long treatment time (8-48 h) was required for Abeta to exert this effect. Western blot analysis revealed that expression level of the glutamate transporter GLAST was increased by treatment with 10-20 microM Abeta for 8-48 h. These results suggest that Abeta upregulates a glutamate uptake system of astrocytes and enhances the clearance of extracellular L-glutamate.
Abe
Kazuho
K
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo 142-8501, Japan. abe@hoshi.ac.jp
Misawa
Miwa
M
D000544:Alzheimer Disease / Q000378:metabolism; D027322:Amino Acid Transport System X-AG / Q000096:biosynthesis; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005110:Extracellular Space; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D027322:Amino Acid Transport System X-AG; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D018698:Glutamic Acid