Literature DB >> 9609401

The glio-toxic mechanism of alpha-aminoadipic acid on cultured astrocytes.

D R Brown1, H A Kretzschmar.   

Abstract

The mechanism of action of the glutamate analogue alpha-aminoadipic (AAA) acid was investigated in terms of its toxicity to cultured astrocytes. AAA was more toxic to type 1 astrocytes than type 2 astrocytes. Also the higher toxicity of the L-isomer as compared to the D-isomer was seen on type 1 astrocytes but not type 2. The toxicity of AAA can be reduced by co-culture of type 1 astrocytes with microglia. This inhibition may be due to glutamate release by microglia. No such effect is seen for type 2 astrocytes. The major uptake route for AAA by type 1 astrocytes is through the sodium dependent glutamate port. Both isomers of AAA are toxic to dividing astrocytes. The D-isomer appears to be toxic only for mitotic cells. The mechanism of this toxicity is protein synthesis dependent. It is suggested that AAA is toxic to mitotic astrocytes by interference with protein synthesis needed for cell division. D-AAA as opposed to L-AAA may prove a valuable tool for investigation of astrocyte proliferation in development and disease.

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Year:  1998        PMID: 9609401     DOI: 10.1023/a:1006947322342

Source DB:  PubMed          Journal:  J Neurocytol        ISSN: 0300-4864


  14 in total

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