Glutamine-mediated protection from neuronal cell death depends on mitochondrial activity
▶ Utilization of glutamine by neuronal mitochondria depends on their functional activity. ▶ Glutamine stimulates glutamate-dependent neuronal damage under impaired respiration. ▶ In neurons with fully functional mitochondria glutamine promotes cell survival. The specific aim of this study was to elu...
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| Veröffentlicht in: | Neuroscience letters 2010-09, Vol.482 (2), p.151-155 |
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| container_title | Neuroscience letters |
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| creator | Stelmashook, E.V. Lozier, E.R. Goryacheva, E.S. Mergenthaler, P. Novikova, S.V. Zorov, D.B. Isaev, N.K. |
| description | ▶ Utilization of glutamine by neuronal mitochondria depends on their functional activity. ▶ Glutamine stimulates glutamate-dependent neuronal damage under impaired respiration. ▶ In neurons with fully functional mitochondria glutamine promotes cell survival.
The specific aim of this study was to elucidate the role of mitochondria in a neuronal death caused by different metabolic effectors and possible role of intracellular calcium ions ([Ca
2+]
i) and glutamine in mitochondria- and non-mitochondria-mediated cell death. Inhibition of mitochondrial complex I by rotenone was found to cause intensive death of cultured cerebellar granule neurons (CGNs) that was preceded by an increase in intracellular calcium concentration ([Ca
2+]
i). The neuronal death induced by rotenone was significantly potentiated by glutamine. In addition, inhibition of Na/K-ATPase by ouabain also caused [Ca
2+]
i increase, but it induced neuronal cell death only in the absence of glucose. Treatment with glutamine prevented the toxic effect of ouabain and decreased [Ca
2+]
i. Blockade of ionotropic glutamate receptors prevented neuronal death and significantly decreased [Ca
2+]
i, demonstrating that toxicity of rotenone and ouabain was at least partially mediated by activation of these receptors. Activation of glutamate receptors by NMDA increased [Ca
2+]
i and decreased mitochondrial membrane potential leading to markedly decreased neuronal survival under glucose deprivation. Glutamine treatment under these conditions prevented cell death and significantly decreased the disturbances of [Ca
2+]
i and changes in mitochondrial membrane potential caused by NMDA during hypoglycemia. Our results indicate that glutamine stimulates glutamate-dependent neuronal damage when mitochondrial respiration is impaired. However, when mitochondria are functionally active, glutamine can be used by mitochondria as an alternative substrate to maintain cellular energy levels and promote cell survival. |
| doi_str_mv | 10.1016/j.neulet.2010.07.022 |
| format | Article |
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The specific aim of this study was to elucidate the role of mitochondria in a neuronal death caused by different metabolic effectors and possible role of intracellular calcium ions ([Ca
2+]
i) and glutamine in mitochondria- and non-mitochondria-mediated cell death. Inhibition of mitochondrial complex I by rotenone was found to cause intensive death of cultured cerebellar granule neurons (CGNs) that was preceded by an increase in intracellular calcium concentration ([Ca
2+]
i). The neuronal death induced by rotenone was significantly potentiated by glutamine. In addition, inhibition of Na/K-ATPase by ouabain also caused [Ca
2+]
i increase, but it induced neuronal cell death only in the absence of glucose. Treatment with glutamine prevented the toxic effect of ouabain and decreased [Ca
2+]
i. Blockade of ionotropic glutamate receptors prevented neuronal death and significantly decreased [Ca
2+]
i, demonstrating that toxicity of rotenone and ouabain was at least partially mediated by activation of these receptors. Activation of glutamate receptors by NMDA increased [Ca
2+]
i and decreased mitochondrial membrane potential leading to markedly decreased neuronal survival under glucose deprivation. Glutamine treatment under these conditions prevented cell death and significantly decreased the disturbances of [Ca
2+]
i and changes in mitochondrial membrane potential caused by NMDA during hypoglycemia. Our results indicate that glutamine stimulates glutamate-dependent neuronal damage when mitochondrial respiration is impaired. However, when mitochondria are functionally active, glutamine can be used by mitochondria as an alternative substrate to maintain cellular energy levels and promote cell survival.</description><identifier>ISSN: 0304-3940</identifier><identifier>EISSN: 1872-7972</identifier><identifier>DOI: 10.1016/j.neulet.2010.07.022</identifier><identifier>PMID: 20650305</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Animals ; Calcium - metabolism ; Cations, Divalent ; Cell Death ; Cells, Cultured ; Cerebellum - cytology ; Electron Transport Complex I - antagonists & inhibitors ; Excitatory Amino Acid Agonists - pharmacology ; Excitatory Amino Acid Antagonists - pharmacology ; Glucose - deficiency ; Glutamine ; Glutamine - pharmacology ; Glutamine - physiology ; Intracellular Space - metabolism ; Membrane Potential, Mitochondrial ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - physiology ; N-Methylaspartate - pharmacology ; Neurons ; Neurons - cytology ; Neurons - drug effects ; Neurons - physiology ; Ouabain - pharmacology ; Rats ; Rats, Wistar ; Rotenone - pharmacology ; Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors</subject><ispartof>Neuroscience letters, 2010-09, Vol.482 (2), p.151-155</ispartof><rights>2010 Elsevier Ireland Ltd</rights><rights>(c) 2010 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-bad55862a5f7e32b357ef3ad1fb30230127f0d660d2b41eb020d68da1138bb353</citedby><cites>FETCH-LOGICAL-c393t-bad55862a5f7e32b357ef3ad1fb30230127f0d660d2b41eb020d68da1138bb353</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0304394010009237$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20650305$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stelmashook, E.V.</creatorcontrib><creatorcontrib>Lozier, E.R.</creatorcontrib><creatorcontrib>Goryacheva, E.S.</creatorcontrib><creatorcontrib>Mergenthaler, P.</creatorcontrib><creatorcontrib>Novikova, S.V.</creatorcontrib><creatorcontrib>Zorov, D.B.</creatorcontrib><creatorcontrib>Isaev, N.K.</creatorcontrib><title>Glutamine-mediated protection from neuronal cell death depends on mitochondrial activity</title><title>Neuroscience letters</title><addtitle>Neurosci Lett</addtitle><description>▶ Utilization of glutamine by neuronal mitochondria depends on their functional activity. ▶ Glutamine stimulates glutamate-dependent neuronal damage under impaired respiration. ▶ In neurons with fully functional mitochondria glutamine promotes cell survival.
The specific aim of this study was to elucidate the role of mitochondria in a neuronal death caused by different metabolic effectors and possible role of intracellular calcium ions ([Ca
2+]
i) and glutamine in mitochondria- and non-mitochondria-mediated cell death. Inhibition of mitochondrial complex I by rotenone was found to cause intensive death of cultured cerebellar granule neurons (CGNs) that was preceded by an increase in intracellular calcium concentration ([Ca
2+]
i). The neuronal death induced by rotenone was significantly potentiated by glutamine. In addition, inhibition of Na/K-ATPase by ouabain also caused [Ca
2+]
i increase, but it induced neuronal cell death only in the absence of glucose. Treatment with glutamine prevented the toxic effect of ouabain and decreased [Ca
2+]
i. Blockade of ionotropic glutamate receptors prevented neuronal death and significantly decreased [Ca
2+]
i, demonstrating that toxicity of rotenone and ouabain was at least partially mediated by activation of these receptors. Activation of glutamate receptors by NMDA increased [Ca
2+]
i and decreased mitochondrial membrane potential leading to markedly decreased neuronal survival under glucose deprivation. Glutamine treatment under these conditions prevented cell death and significantly decreased the disturbances of [Ca
2+]
i and changes in mitochondrial membrane potential caused by NMDA during hypoglycemia. Our results indicate that glutamine stimulates glutamate-dependent neuronal damage when mitochondrial respiration is impaired. However, when mitochondria are functionally active, glutamine can be used by mitochondria as an alternative substrate to maintain cellular energy levels and promote cell survival.</description><subject>Animals</subject><subject>Calcium - metabolism</subject><subject>Cations, Divalent</subject><subject>Cell Death</subject><subject>Cells, Cultured</subject><subject>Cerebellum - cytology</subject><subject>Electron Transport Complex I - antagonists & inhibitors</subject><subject>Excitatory Amino Acid Agonists - pharmacology</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Glucose - deficiency</subject><subject>Glutamine</subject><subject>Glutamine - pharmacology</subject><subject>Glutamine - physiology</subject><subject>Intracellular Space - metabolism</subject><subject>Membrane Potential, Mitochondrial</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - physiology</subject><subject>N-Methylaspartate - pharmacology</subject><subject>Neurons</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - physiology</subject><subject>Ouabain - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Rotenone - pharmacology</subject><subject>Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors</subject><issn>0304-3940</issn><issn>1872-7972</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQhoMoun78A5HePHWdJE2zexFE_IIFLwreQtpMMUvbrEkq-O-dZdWjl4Qkz8w7eRg75zDnwOur9XzEqcc8F0BXoOcgxB6b8YUWpV5qsc9mIKEq5bKCI3ac0hoAFFfVITsSUCt6VDP29tBP2Q5-xHJA521GV2xiyNhmH8aii2EoKCeG0fZFi31fOLT5ndYNji4VxAw-h_Y9jC56YiwVfvr8dcoOOtsnPPvZT9jr_d3L7WO5en54ur1Zla1cylw21im1qIVVnUYpGqk0dtI63jUShAQudAeursGJpuLYgKDTwlnO5aIhWp6wy11fmvpjwpTN4NN2UDtimJJZguZKSC2IrHZkG0NKETuziX6w8ctwMFulZm12Ss1WqQFtSCmVXfwETA0p-iv6dUjA9Q5A-uanx2hS63FsSWckjcYF_3_CN8Rbiq4</recordid><startdate>20100927</startdate><enddate>20100927</enddate><creator>Stelmashook, E.V.</creator><creator>Lozier, E.R.</creator><creator>Goryacheva, E.S.</creator><creator>Mergenthaler, P.</creator><creator>Novikova, S.V.</creator><creator>Zorov, D.B.</creator><creator>Isaev, N.K.</creator><general>Elsevier Ireland Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope></search><sort><creationdate>20100927</creationdate><title>Glutamine-mediated protection from neuronal cell death depends on mitochondrial activity</title><author>Stelmashook, E.V. ; Lozier, E.R. ; Goryacheva, E.S. ; Mergenthaler, P. ; Novikova, S.V. ; Zorov, D.B. ; Isaev, N.K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-bad55862a5f7e32b357ef3ad1fb30230127f0d660d2b41eb020d68da1138bb353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Calcium - metabolism</topic><topic>Cations, Divalent</topic><topic>Cell Death</topic><topic>Cells, Cultured</topic><topic>Cerebellum - cytology</topic><topic>Electron Transport Complex I - antagonists & inhibitors</topic><topic>Excitatory Amino Acid Agonists - pharmacology</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Glucose - deficiency</topic><topic>Glutamine</topic><topic>Glutamine - pharmacology</topic><topic>Glutamine - physiology</topic><topic>Intracellular Space - metabolism</topic><topic>Membrane Potential, Mitochondrial</topic><topic>Mitochondria</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - physiology</topic><topic>N-Methylaspartate - pharmacology</topic><topic>Neurons</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neurons - physiology</topic><topic>Ouabain - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Rotenone - pharmacology</topic><topic>Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stelmashook, E.V.</creatorcontrib><creatorcontrib>Lozier, E.R.</creatorcontrib><creatorcontrib>Goryacheva, E.S.</creatorcontrib><creatorcontrib>Mergenthaler, P.</creatorcontrib><creatorcontrib>Novikova, S.V.</creatorcontrib><creatorcontrib>Zorov, D.B.</creatorcontrib><creatorcontrib>Isaev, N.K.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Neuroscience letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stelmashook, E.V.</au><au>Lozier, E.R.</au><au>Goryacheva, E.S.</au><au>Mergenthaler, P.</au><au>Novikova, S.V.</au><au>Zorov, D.B.</au><au>Isaev, N.K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glutamine-mediated protection from neuronal cell death depends on mitochondrial activity</atitle><jtitle>Neuroscience letters</jtitle><addtitle>Neurosci Lett</addtitle><date>2010-09-27</date><risdate>2010</risdate><volume>482</volume><issue>2</issue><spage>151</spage><epage>155</epage><pages>151-155</pages><issn>0304-3940</issn><eissn>1872-7972</eissn><abstract>▶ Utilization of glutamine by neuronal mitochondria depends on their functional activity. ▶ Glutamine stimulates glutamate-dependent neuronal damage under impaired respiration. ▶ In neurons with fully functional mitochondria glutamine promotes cell survival.
The specific aim of this study was to elucidate the role of mitochondria in a neuronal death caused by different metabolic effectors and possible role of intracellular calcium ions ([Ca
2+]
i) and glutamine in mitochondria- and non-mitochondria-mediated cell death. Inhibition of mitochondrial complex I by rotenone was found to cause intensive death of cultured cerebellar granule neurons (CGNs) that was preceded by an increase in intracellular calcium concentration ([Ca
2+]
i). The neuronal death induced by rotenone was significantly potentiated by glutamine. In addition, inhibition of Na/K-ATPase by ouabain also caused [Ca
2+]
i increase, but it induced neuronal cell death only in the absence of glucose. Treatment with glutamine prevented the toxic effect of ouabain and decreased [Ca
2+]
i. Blockade of ionotropic glutamate receptors prevented neuronal death and significantly decreased [Ca
2+]
i, demonstrating that toxicity of rotenone and ouabain was at least partially mediated by activation of these receptors. Activation of glutamate receptors by NMDA increased [Ca
2+]
i and decreased mitochondrial membrane potential leading to markedly decreased neuronal survival under glucose deprivation. Glutamine treatment under these conditions prevented cell death and significantly decreased the disturbances of [Ca
2+]
i and changes in mitochondrial membrane potential caused by NMDA during hypoglycemia. Our results indicate that glutamine stimulates glutamate-dependent neuronal damage when mitochondrial respiration is impaired. However, when mitochondria are functionally active, glutamine can be used by mitochondria as an alternative substrate to maintain cellular energy levels and promote cell survival.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>20650305</pmid><doi>10.1016/j.neulet.2010.07.022</doi><tpages>5</tpages></addata></record> |
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| ispartof | Neuroscience letters, 2010-09, Vol.482 (2), p.151-155 |
| issn | 0304-3940 1872-7972 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Calcium - metabolism Cations, Divalent Cell Death Cells, Cultured Cerebellum - cytology Electron Transport Complex I - antagonists & inhibitors Excitatory Amino Acid Agonists - pharmacology Excitatory Amino Acid Antagonists - pharmacology Glucose - deficiency Glutamine Glutamine - pharmacology Glutamine - physiology Intracellular Space - metabolism Membrane Potential, Mitochondrial Mitochondria Mitochondria - drug effects Mitochondria - physiology N-Methylaspartate - pharmacology Neurons Neurons - cytology Neurons - drug effects Neurons - physiology Ouabain - pharmacology Rats Rats, Wistar Rotenone - pharmacology Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors |
| title | Glutamine-mediated protection from neuronal cell death depends on mitochondrial activity |
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