Protection against glucose-induced neuronal death by NAAG and GCP II inhibition is regulated by mGluR3
| Autor: | Amanda M. Robinson, David Golovoy, Barbara S. Slusher, Alison Berent-Spillson, James W. Russell, Camilo Rojas |
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| Rok vydání: | 2004 |
| Předmět: |
Agonist
Glutamate Carboxypeptidase II medicine.medical_specialty Programmed cell death Neurite medicine.drug_class Apoptosis Biology Receptors Metabotropic Glutamate Biochemistry Neuroprotection Rats Sprague-Dawley Cellular and Molecular Neuroscience Organophosphorus Compounds Dorsal root ganglion Diabetic Neuropathies Internal medicine Ganglia Spinal medicine Glutamate carboxypeptidase II Neurites Animals Enzyme Inhibitors Cells Cultured Neurons Dose-Response Relationship Drug Antagonist Dipeptides Coculture Techniques Rats medicine.anatomical_structure Endocrinology Glucose Neuroprotective Agents Metabotropic glutamate receptor Schwann Cells Excitatory Amino Acid Antagonists |
| Zdroj: | Journal of neurochemistry. 89(1) |
| ISSN: | 0022-3042 |
| Popis: | Glutamate carboxypeptidase II (GCP II) inhibition has previously been shown to be protective against long-term neuropathy in diabetic animals. In the current study, we have determined that the GCP II inhibitor 2-(phosphonomethyl) pentanedioic acid (2-PMPA) is protective against glucose-induced programmed cell death (PCD) and neurite degeneration in dorsal root ganglion (DRG) neurons in a cell culture model of diabetic neuropathy. In this model, inhibition of caspase activation is mediated through the group II metabotropic glutamate receptor, mGluR3. 2-PMPA neuroprotection is completely reversed by the mGluR3 antagonist (S)-alpha-ethylglutamic acid (EGLU). In contrast, group I and III mGluR inhibitors have no effect on 2-PMPA neuroprotection. Furthermore, we show that two mGluR3 agonists, the direct agonist (2R,4R)-4-aminopyrrolidine-2, 4-dicarboxylate (APDC) and N-acetyl-aspartyl-glutamate (NAAG) provide protection to neurons exposed to high glucose conditions, consistent with the concept that 2-PMPA neuroprotection is mediated by increased NAAG activity. Inhibition of GCP II or mGluR3 may represent a novel mechanism to treat neuronal degeneration under high-glucose conditions. |
| Databáze: | OpenAIRE |
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