Neuroprotection mediated by subtoxic dose of NMDA in SH-SY5Y neuroblastoma cultures: activity-dependent regulation of PSA-NCAM expression.

Abstract

The NMDA class of glutamate receptors plays a critical role in CNS, such as synaptic plasticity, axonal sprouting, growth, and migration. NMDA receptor stimulation has been shown to regulate polysialylated neural cell adhesion molecule (PSA-NCAM) expression in glial cell cultures and in hippocampal slice cultures. There is also growing evidence that molecular chaperons and ROS are related to the synaptic plasticity phenomena. We have examined the neuroprotective effect of subtoxic dose of NMDA in retinoic acid differentiated SH-SY5Y neuroblastoma cells. SH-SY5Y cell line differentiated with retinoic acid (10 muM) was exposed to NMDA (100 microM) or to antagonist MK-801 (200 nM) + NMDA and cells harvested after 24 h of treatment for PSA-NCAM, NCAM, and HSP70 expression study and for biochemical analysis. A significant increase was observed in PSA-NCAM, NCAM-180, NCAM-140, and HSP70 expression as seen by Western blotting and immunocytofluorescent studies in NMDA-treated cultures. Biochemical analysis revealed a significant increase in the activities of glutathione peroxidase (GPx) and copper zinc-superoxide dismutase (CuZnSOD) upon exposure to NMDA. No significant change was observed in the level of lipid peroxidation. All the changes observed reverted back to the control values upon pretreatment of cultures with MK-801, a non-competitive NMDA receptor antagonist, prior to NMDA exposure indicating the involvement of NMDA receptor in these changes. These results illustrate the neuroprotective role of subtoxic dose of NMDA in SH-SY5Y neuroblastoma cells.

• Authors: Jaspreet Singh, Gurcharan Kaur
• Journal: Brain research. Molecular brain research (Brain Res Mol Brain Res) Vol. 137 Issue 1-2 Pg. 223-34 (Jun 13 2005) ISSN: 0169-328X [Print] Netherlands
• PMID: 15950781 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Excitatory Amino Acid Agonists
• Excitatory Amino Acid Antagonists
• Free Radical Scavengers
• HSP70 Heat-Shock Proteins
• Neural Cell Adhesion Molecule L1
• Neural Cell Adhesion Molecules
• Neuroprotective Agents
• Receptors, N-Methyl-D-Aspartate
• SOD1 protein, human
• Sialic Acids
• polysialyl neural cell adhesion molecule
• Tretinoin
• N-Methylaspartate
• Glutathione Peroxidase
• Superoxide Dismutase
• Superoxide Dismutase-1

Topics

• Brain (drug effects, metabolism)
• Cell Survival (drug effects, physiology)
• Cytoprotection (drug effects, physiology)
• Dose-Response Relationship, Drug
• Excitatory Amino Acid Agonists (pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology)
• Free Radical Scavengers (metabolism)
• Glutathione Peroxidase (drug effects, metabolism)
• HSP70 Heat-Shock Proteins (drug effects, metabolism)
• Humans
• Lipid Peroxidation (drug effects, physiology)
• N-Methylaspartate (pharmacology)
• Neural Cell Adhesion Molecule L1 (drug effects, metabolism)
• Neural Cell Adhesion Molecules (drug effects, metabolism)
• Neuroblastoma
• Neuronal Plasticity (drug effects, physiology)
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects, physiology)
• Receptors, N-Methyl-D-Aspartate (agonists, metabolism)
• Sialic Acids (metabolism)
• Superoxide Dismutase (drug effects, metabolism)
• Superoxide Dismutase-1
• Tretinoin (pharmacology)
• Tumor Cells, Cultured