Low Dose Administration of Glutamate Triggers a Non-Apoptotic, Autophagic Response in PC12 Cells
Background/Aims: Increasing amounts of the neurotransmitter glutamate are associated with excitotoxicity, a phenomenon related both to homeostatic processes and neurodegenerative diseases such as multiple sclerosis. Methods: PC12 cells (rat pheochromocytoma) were treated with various concentrations...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2015-11-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/430250 |
| _version_ | 1818014263509254144 |
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| author | Eleni Stamoula Theofanis Vavilis Eleni Aggelidou Aikaterini Kaidoglou Angeliki Cheva Kyriakos Mellidis Antigone Lazou Costas Haitoglou Maria Albani Aristeidis Kritis |
| author_facet | Eleni Stamoula Theofanis Vavilis Eleni Aggelidou Aikaterini Kaidoglou Angeliki Cheva Kyriakos Mellidis Antigone Lazou Costas Haitoglou Maria Albani Aristeidis Kritis |
| author_sort | Eleni Stamoula |
| collection | DOAJ |
| description | Background/Aims: Increasing amounts of the neurotransmitter glutamate are associated with excitotoxicity, a phenomenon related both to homeostatic processes and neurodegenerative diseases such as multiple sclerosis. Methods: PC12 cells (rat pheochromocytoma) were treated with various concentrations of the non-essential amino acid glutamate for 0.5-24 hours. The effect of glutamate on cell morphology was monitored with electron microscopy and haematoxylin-eosin staining. Cell survival was calculated with the MTT assay. Expression analysis of chaperones associated with the observed phenotype was performed using either Western Blotting at the protein level or qRT-PCR at the mRNA level. Results: Administration of glutamate in PC12 cells in doses as low as 10 μM causes an up-regulation of GRP78, GRP94 and HSC70 protein levels, while their mRNA levels show the opposite kinetics. At the same time, GAPDH and GRP75 show reduced protein levels, irrespective of their transcriptional rate. On a cellular level, low concentrations of glutamate induce an autophagy-mediated pro-survival phenotype, which is further supported by induction of the autophagic marker LC3. Conclusion: The findings in the present study underline a discrete effect of glutamate on neuronal cell fate depending on its concentration. It was also shown that a low dose of glutamate orchestrates a unique expression signature of various chaperones and induces cell autophagy, which acts in a neuroprotective fashion. |
| first_indexed | 2024-04-14T06:42:48Z |
| format | Article |
| id | doaj.art-4ef4e43ec0dd4ed79ee172fd754edba7 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-14T06:42:48Z |
| publishDate | 2015-11-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-4ef4e43ec0dd4ed79ee172fd754edba72022-12-22T02:07:16ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-11-013751750175810.1159/000430250430250Low Dose Administration of Glutamate Triggers a Non-Apoptotic, Autophagic Response in PC12 CellsEleni StamoulaTheofanis VavilisEleni AggelidouAikaterini KaidoglouAngeliki ChevaKyriakos MellidisAntigone LazouCostas HaitoglouMaria AlbaniAristeidis KritisBackground/Aims: Increasing amounts of the neurotransmitter glutamate are associated with excitotoxicity, a phenomenon related both to homeostatic processes and neurodegenerative diseases such as multiple sclerosis. Methods: PC12 cells (rat pheochromocytoma) were treated with various concentrations of the non-essential amino acid glutamate for 0.5-24 hours. The effect of glutamate on cell morphology was monitored with electron microscopy and haematoxylin-eosin staining. Cell survival was calculated with the MTT assay. Expression analysis of chaperones associated with the observed phenotype was performed using either Western Blotting at the protein level or qRT-PCR at the mRNA level. Results: Administration of glutamate in PC12 cells in doses as low as 10 μM causes an up-regulation of GRP78, GRP94 and HSC70 protein levels, while their mRNA levels show the opposite kinetics. At the same time, GAPDH and GRP75 show reduced protein levels, irrespective of their transcriptional rate. On a cellular level, low concentrations of glutamate induce an autophagy-mediated pro-survival phenotype, which is further supported by induction of the autophagic marker LC3. Conclusion: The findings in the present study underline a discrete effect of glutamate on neuronal cell fate depending on its concentration. It was also shown that a low dose of glutamate orchestrates a unique expression signature of various chaperones and induces cell autophagy, which acts in a neuroprotective fashion.http://www.karger.com/Article/FullText/430250autophagyGlutamateChaperonesStressExcitotoxicity |
| spellingShingle | Eleni Stamoula Theofanis Vavilis Eleni Aggelidou Aikaterini Kaidoglou Angeliki Cheva Kyriakos Mellidis Antigone Lazou Costas Haitoglou Maria Albani Aristeidis Kritis Low Dose Administration of Glutamate Triggers a Non-Apoptotic, Autophagic Response in PC12 Cells Cellular Physiology and Biochemistry autophagy Glutamate Chaperones Stress Excitotoxicity |
| title | Low Dose Administration of Glutamate Triggers a Non-Apoptotic, Autophagic Response in PC12 Cells |
| title_full | Low Dose Administration of Glutamate Triggers a Non-Apoptotic, Autophagic Response in PC12 Cells |
| title_fullStr | Low Dose Administration of Glutamate Triggers a Non-Apoptotic, Autophagic Response in PC12 Cells |
| title_full_unstemmed | Low Dose Administration of Glutamate Triggers a Non-Apoptotic, Autophagic Response in PC12 Cells |
| title_short | Low Dose Administration of Glutamate Triggers a Non-Apoptotic, Autophagic Response in PC12 Cells |
| title_sort | low dose administration of glutamate triggers a non apoptotic autophagic response in pc12 cells |
| topic | autophagy Glutamate Chaperones Stress Excitotoxicity |
| url | http://www.karger.com/Article/FullText/430250 |
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