Mouse galectin-1 inhibits the toxicity of glutamate by modifying NR1 NMDA receptor expression.
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.
Lekishvili
Tamuna
T
Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK.
Hesketh
Shirley
S
Brazier
Marcus W
MW
Brown
David R
DR
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018920:Coculture Techniques; D037483:Galectin 1 / Q000378:metabolism / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity*; D051379:Mice; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D037483:Galectin 1; C473649:NR1A NMDA receptor, rat; D018696:Neuroprotective Agents; D009498:Neurotoxins; D020319:Oligodeoxyribonucleotides, Antisense; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D011493:Protein Kinase C