Protection against glucose-induced neuronal death by NAAG and GCP II inhibition is regulated by mGluR3
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.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2004 |
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| Erschienen: |
2004 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:89 |
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| Enthalten in: |
Journal of neurochemistry - 89(2004), 1 vom: 01. Apr., Seite 90-9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Berent-Spillson, Alison [VerfasserIn] |
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| Anmerkungen: |
Date Completed 26.04.2004 Date Revised 24.11.2016 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM14729245X |
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| 100 | 1 | |a Berent-Spillson, Alison |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Protection against glucose-induced neuronal death by NAAG and GCP II inhibition is regulated by mGluR3 |
| 264 | 1 | |c 2004 | |
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| 500 | |a Date Revised 24.11.2016 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 7 | |a 2-(phosphonomethyl)pentanedioic acid |2 NLM | |
| 650 | 7 | |a Dipeptides |2 NLM | |
| 650 | 7 | |a Enzyme Inhibitors |2 NLM | |
| 650 | 7 | |a Excitatory Amino Acid Antagonists |2 NLM | |
| 650 | 7 | |a Neuroprotective Agents |2 NLM | |
| 650 | 7 | |a Organophosphorus Compounds |2 NLM | |
| 650 | 7 | |a Receptors, Metabotropic Glutamate |2 NLM | |
| 650 | 7 | |a metabotropic glutamate receptor 3 |2 NLM | |
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| 700 | 1 | |a Robinson, Amanda M |e verfasserin |4 aut | |
| 700 | 1 | |a Golovoy, David |e verfasserin |4 aut | |
| 700 | 1 | |a Slusher, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Rojas, Camilo |e verfasserin |4 aut | |
| 700 | 1 | |a Russell, James W |e verfasserin |4 aut | |
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