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Glyoxal inactivates glutamate transporter‐1 in cultured rat astrocytes
Author(s) -
Kawaguchi Motoko,
Shibata Noriyuki,
Horiuchi Seikoh,
Kobayashi Makio
Publication year - 2005
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/j.1440-1789.2004.00579.x
Subject(s) - glyoxal , glutamate receptor , amyotrophic lateral sclerosis , chemistry , motor neuron , riluzole , astrocyte , neuron , lysine , microbiology and biotechnology , biochemistry , biology , medicine , neuroscience , amino acid , central nervous system , receptor , disease , organic chemistry , spinal cord
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive motor paralysis and selective motor neuron death. There is increasing evidence that motor neuron death in ALS is mediated by glutamate toxicity resulting from reduced activity of astrocytic glutamate transporter‐1 (GLT‐1). Recent morphological studies have shown that N ɛ ‐(carboxymethyl)lysine (CML) accumulates in reactive astrocytes of ALS spinal cords. CML is a product of post‐translational protein modification by glyoxal, a reactive aldehydic intermediate. In considering these documents, it is important to determine whether GLT‐1 protein modification by glyoxal might cause reduced GLT‐1 activity. To address this issue, we investigated the effects of glyoxal on GLT‐1 properties in cultured rat astrocytes. High performance liquid chromatography showed reduced glutamate uptake activity in the glyoxal‐exposed cells. Immunocytochemical analysis displayed CML accumulation in the cytoplasm of astrocytes by glyoxal exposure. Immunoblots of immunoprecipitated GLT‐1 disclosed GLT‐1 CML adduct formation in the glyoxal‐exposed cells. Our results indicate that glyoxal modifies GLT‐1 to form CML and simultaneously deprives its glutamate uptake activity. Thus, these toxic effects of glyoxal on astrocytes might be implicated in motor neuron death in ALS.