Dexamethasone-enhanced sensitivity of mouse hippocampal HT22 cells for oxidative stress is associated with the suppression of nuclear factor-kappaB
Glucocorticoids (GCs) exacerbate various insults to the hippocampus but the exact molecular mechanisms of this GC activity is not known. GCs can suppress the activity of the redox-sensitive nuclear factor NF-kappaB, which potentially serves neuroprotective functions. Employing electrophoretic mobili...
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| Veröffentlicht in: | Neuroscience letters 2000-12, Vol.295 (3), p.101 |
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| creator | Braun, S Liebetrau, W Berning, B Behl, C |
| description | Glucocorticoids (GCs) exacerbate various insults to the hippocampus but the exact molecular mechanisms of this GC activity is not known. GCs can suppress the activity of the redox-sensitive nuclear factor NF-kappaB, which potentially serves neuroprotective functions. Employing electrophoretic mobility shift assays and transfection assays using a NF-kappaB-dependent reporter plasmid, we demonstrate that the increased oxidative stress sensitivity of clonal mouse hippocampal HT22 cells caused by GCs is associated with the suppression of NF-kappaB. GCs increased the expression of IkappaBalpha, the physiological inhibitor of NF-kappaB. Downregulation of NF-kappaB activity after overexpression of a dominant-negative mutant form of IkappaBalpha results in an increased sensitivity to oxidative stress. We conclude that the suppression of the basal NF-kappaB activity contributes to the enhanced vulnerability of neuronal cells to oxidative stress caused by GCs. |
| format | Article |
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GCs can suppress the activity of the redox-sensitive nuclear factor NF-kappaB, which potentially serves neuroprotective functions. Employing electrophoretic mobility shift assays and transfection assays using a NF-kappaB-dependent reporter plasmid, we demonstrate that the increased oxidative stress sensitivity of clonal mouse hippocampal HT22 cells caused by GCs is associated with the suppression of NF-kappaB. GCs increased the expression of IkappaBalpha, the physiological inhibitor of NF-kappaB. Downregulation of NF-kappaB activity after overexpression of a dominant-negative mutant form of IkappaBalpha results in an increased sensitivity to oxidative stress. We conclude that the suppression of the basal NF-kappaB activity contributes to the enhanced vulnerability of neuronal cells to oxidative stress caused by GCs.</description><identifier>ISSN: 0304-3940</identifier><identifier>PMID: 11090984</identifier><language>eng</language><publisher>Ireland</publisher><subject>Animals ; Cell Survival - drug effects ; Cell Survival - genetics ; Cells, Cultured - cytology ; Cells, Cultured - drug effects ; Cells, Cultured - metabolism ; Dexamethasone - toxicity ; DNA-Binding Proteins - drug effects ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Down-Regulation - drug effects ; Down-Regulation - physiology ; Hippocampus - cytology ; Hippocampus - drug effects ; Hippocampus - metabolism ; Mice ; Neurons - cytology ; Neurons - drug effects ; Neurons - metabolism ; NF-kappa B - drug effects ; NF-kappa B - metabolism ; Oxidative Stress - drug effects ; Oxidative Stress - physiology ; Promoter Regions, Genetic - drug effects ; Promoter Regions, Genetic - physiology ; Receptors, Glucocorticoid - drug effects ; Receptors, Glucocorticoid - metabolism ; Transcription, Genetic - drug effects ; Transcription, Genetic - physiology ; Transfection</subject><ispartof>Neuroscience letters, 2000-12, Vol.295 (3), p.101</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11090984$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Braun, S</creatorcontrib><creatorcontrib>Liebetrau, W</creatorcontrib><creatorcontrib>Berning, B</creatorcontrib><creatorcontrib>Behl, C</creatorcontrib><title>Dexamethasone-enhanced sensitivity of mouse hippocampal HT22 cells for oxidative stress is associated with the suppression of nuclear factor-kappaB</title><title>Neuroscience letters</title><addtitle>Neurosci Lett</addtitle><description>Glucocorticoids (GCs) exacerbate various insults to the hippocampus but the exact molecular mechanisms of this GC activity is not known. GCs can suppress the activity of the redox-sensitive nuclear factor NF-kappaB, which potentially serves neuroprotective functions. Employing electrophoretic mobility shift assays and transfection assays using a NF-kappaB-dependent reporter plasmid, we demonstrate that the increased oxidative stress sensitivity of clonal mouse hippocampal HT22 cells caused by GCs is associated with the suppression of NF-kappaB. GCs increased the expression of IkappaBalpha, the physiological inhibitor of NF-kappaB. Downregulation of NF-kappaB activity after overexpression of a dominant-negative mutant form of IkappaBalpha results in an increased sensitivity to oxidative stress. We conclude that the suppression of the basal NF-kappaB activity contributes to the enhanced vulnerability of neuronal cells to oxidative stress caused by GCs.</description><subject>Animals</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - genetics</subject><subject>Cells, Cultured - cytology</subject><subject>Cells, Cultured - drug effects</subject><subject>Cells, Cultured - metabolism</subject><subject>Dexamethasone - toxicity</subject><subject>DNA-Binding Proteins - drug effects</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Down-Regulation - drug effects</subject><subject>Down-Regulation - physiology</subject><subject>Hippocampus - cytology</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Mice</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>NF-kappa B - drug effects</subject><subject>NF-kappa B - metabolism</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxidative Stress - physiology</subject><subject>Promoter Regions, Genetic - drug effects</subject><subject>Promoter Regions, Genetic - physiology</subject><subject>Receptors, Glucocorticoid - drug effects</subject><subject>Receptors, Glucocorticoid - metabolism</subject><subject>Transcription, Genetic - drug effects</subject><subject>Transcription, Genetic - physiology</subject><subject>Transfection</subject><issn>0304-3940</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kE1OwzAQhbMA0VK4AvIFIo0TW02WUH6KVIlN99XEHiuGJLYyDrTn4MKkAlZv8T190nsX2RJKUHlZK1hk18zvAKClVlfZQkqooa7UMvt-pCP2lFrkMFBOQ4uDISuYBvbJf_p0EsGJPkxMovUxBoN9xE5s90UhDHUdCxdGEY7e4twnwWkkZuFZIHMwHtOs-_KpFamd6RTjmfswnL3DZDrCUTg0KYz5B8aIDzfZpcOO6fYvV9n--Wm_2ea7t5fXzf0uj1qpHCsLyoGS0BinGwU1ypqgNKWt1gbQKqUbXWk0rllbJ01hUdK822k9A1musrtfbZyanuwhjr7H8XT4P6f8AVU7Y9E</recordid><startdate>20001208</startdate><enddate>20001208</enddate><creator>Braun, S</creator><creator>Liebetrau, W</creator><creator>Berning, B</creator><creator>Behl, C</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20001208</creationdate><title>Dexamethasone-enhanced sensitivity of mouse hippocampal HT22 cells for oxidative stress is associated with the suppression of nuclear factor-kappaB</title><author>Braun, S ; Liebetrau, W ; Berning, B ; Behl, C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p544-a8d04f0410bcf5b409a19e03c3d87c0ad445b585acfb7df1c2da1e090f555b513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - genetics</topic><topic>Cells, Cultured - cytology</topic><topic>Cells, Cultured - drug effects</topic><topic>Cells, Cultured - metabolism</topic><topic>Dexamethasone - toxicity</topic><topic>DNA-Binding Proteins - drug effects</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Down-Regulation - drug effects</topic><topic>Down-Regulation - physiology</topic><topic>Hippocampus - cytology</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Mice</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>NF-kappa B - drug effects</topic><topic>NF-kappa B - metabolism</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxidative Stress - physiology</topic><topic>Promoter Regions, Genetic - drug effects</topic><topic>Promoter Regions, Genetic - physiology</topic><topic>Receptors, Glucocorticoid - drug effects</topic><topic>Receptors, Glucocorticoid - metabolism</topic><topic>Transcription, Genetic - drug effects</topic><topic>Transcription, Genetic - physiology</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Braun, S</creatorcontrib><creatorcontrib>Liebetrau, W</creatorcontrib><creatorcontrib>Berning, B</creatorcontrib><creatorcontrib>Behl, C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Neuroscience letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Braun, S</au><au>Liebetrau, W</au><au>Berning, B</au><au>Behl, C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dexamethasone-enhanced sensitivity of mouse hippocampal HT22 cells for oxidative stress is associated with the suppression of nuclear factor-kappaB</atitle><jtitle>Neuroscience letters</jtitle><addtitle>Neurosci Lett</addtitle><date>2000-12-08</date><risdate>2000</risdate><volume>295</volume><issue>3</issue><spage>101</spage><pages>101-</pages><issn>0304-3940</issn><abstract>Glucocorticoids (GCs) exacerbate various insults to the hippocampus but the exact molecular mechanisms of this GC activity is not known. GCs can suppress the activity of the redox-sensitive nuclear factor NF-kappaB, which potentially serves neuroprotective functions. Employing electrophoretic mobility shift assays and transfection assays using a NF-kappaB-dependent reporter plasmid, we demonstrate that the increased oxidative stress sensitivity of clonal mouse hippocampal HT22 cells caused by GCs is associated with the suppression of NF-kappaB. GCs increased the expression of IkappaBalpha, the physiological inhibitor of NF-kappaB. Downregulation of NF-kappaB activity after overexpression of a dominant-negative mutant form of IkappaBalpha results in an increased sensitivity to oxidative stress. We conclude that the suppression of the basal NF-kappaB activity contributes to the enhanced vulnerability of neuronal cells to oxidative stress caused by GCs.</abstract><cop>Ireland</cop><pmid>11090984</pmid></addata></record> |
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| identifier | ISSN: 0304-3940 |
| ispartof | Neuroscience letters, 2000-12, Vol.295 (3), p.101 |
| issn | 0304-3940 |
| language | eng |
| recordid | cdi_pubmed_primary_11090984 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Cell Survival - drug effects Cell Survival - genetics Cells, Cultured - cytology Cells, Cultured - drug effects Cells, Cultured - metabolism Dexamethasone - toxicity DNA-Binding Proteins - drug effects DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Down-Regulation - drug effects Down-Regulation - physiology Hippocampus - cytology Hippocampus - drug effects Hippocampus - metabolism Mice Neurons - cytology Neurons - drug effects Neurons - metabolism NF-kappa B - drug effects NF-kappa B - metabolism Oxidative Stress - drug effects Oxidative Stress - physiology Promoter Regions, Genetic - drug effects Promoter Regions, Genetic - physiology Receptors, Glucocorticoid - drug effects Receptors, Glucocorticoid - metabolism Transcription, Genetic - drug effects Transcription, Genetic - physiology Transfection |
| title | Dexamethasone-enhanced sensitivity of mouse hippocampal HT22 cells for oxidative stress is associated with the suppression of nuclear factor-kappaB |
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