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Mouse galectin‐1 inhibits the toxicity of glutamate by modifying NR1 NMDA receptor expression
Author(s) -
Lekishvili Tamuna,
Hesketh Shirley,
Brazier Marcus W.,
Brown David R.
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.05207.x
Subject(s) - excitotoxicity , glutamate receptor , neuroprotection , nmda receptor , astrocyte , neurotoxicity , biology , receptor , microbiology and biotechnology , programmed cell death , pharmacology , toxicity , chemistry , biochemistry , neuroscience , apoptosis , central nervous system , organic chemistry
One of the major causes of neuronal death in neurodegenerative disease is excitotoxicity from the neurotransmitter glutamate. This form of cell death could arise from either excess levels of glutamate due to decreased astrocyte clearance or due to increased susceptibility. We have identified galectin‐1, a galactose‐binding lectin, as a potential neuroprotective factor secreted by astrocytes. Our results show that both native and recombinant galectin‐1 protects mouse and rat cerebellar neurons from the toxic effects of glutamate. Galectin‐1 applied to neurons increased their expression of the NMDA receptor NR1 and increased the proportion of the NR1a subunit subtype while antisense knockdown of the NR1a receptor blocked the neuroprotective effect of galectin‐1. This effect of the protein was dependent upon it carbohydrate recognition domain, suggesting that the protein acts in a reduced dimerized form. In addition, galectin‐1 caused a decreased expression of PKC associated with increased resistance to glutamate toxicity. These results suggest that the astrocytic lectin galectin‐1 could protect neurons against the effects of excitotoxicity as seen in stroke and ischemic injury.