Minocycline attenuates iron neurotoxicity in cortical cell cultures
Iron neurotoxicity may contribute to the pathogenesis of intracerebral hemorrhage (ICH). The tetracycline derivative minocycline is protective in ICH models, due putatively to inhibition of microglial activation. Although minocycline also chelates iron, its effect on iron neurotoxicity has not been...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2009-08, Vol.386 (2), p.322-326 |
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| creator | Chen-Roetling, Jing Chen, Lifen Regan, Raymond F. |
| description | Iron neurotoxicity may contribute to the pathogenesis of intracerebral hemorrhage (ICH). The tetracycline derivative minocycline is protective in ICH models, due putatively to inhibition of microglial activation. Although minocycline also chelates iron, its effect on iron neurotoxicity has not been reported, and was examined in this study. Cortical cultures treated with 10
μM ferrous sulfate for 24
h sustained loss of most neurons and an increase in malondialdehyde. Minocycline prevented this injury, with near-complete protection at 30
μM. Two other inhibitors of microglial activation, doxycycline and macrophage/microglia inhibitory factor, were ineffective. Oxidation of isolated culture membranes by iron was also inhibited by minocycline. Consistent with prior observations, minocycline chelated iron in a siderophore colorometric assay; at concentrations less than 100
μM, its activity exceeded that of deferoxamine. These results suggest that attenuation of iron neurotoxicity may contribute to the beneficial effect of minocycline in hemorrhagic stroke and other CNS injury models. |
| doi_str_mv | 10.1016/j.bbrc.2009.06.026 |
| format | Article |
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μM ferrous sulfate for 24
h sustained loss of most neurons and an increase in malondialdehyde. Minocycline prevented this injury, with near-complete protection at 30
μM. Two other inhibitors of microglial activation, doxycycline and macrophage/microglia inhibitory factor, were ineffective. Oxidation of isolated culture membranes by iron was also inhibited by minocycline. Consistent with prior observations, minocycline chelated iron in a siderophore colorometric assay; at concentrations less than 100
μM, its activity exceeded that of deferoxamine. These results suggest that attenuation of iron neurotoxicity may contribute to the beneficial effect of minocycline in hemorrhagic stroke and other CNS injury models.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2009.06.026</identifier><identifier>PMID: 19523448</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Cell culture ; Cerebral Cortex - cytology ; Cerebral Cortex - drug effects ; Cerebral Hemorrhage - complications ; Cytoprotection ; Deferoxamine - pharmacology ; Free radical ; Hemoglobin toxicity ; Inflammation ; Intracerebral hemorrhage ; Iron - toxicity ; Iron Chelating Agents - pharmacology ; Mice ; Mice, Inbred Strains ; Minocycline - pharmacology ; Mouse ; Neurons - drug effects ; Neuroprotective Agents - pharmacology ; Neurotoxicity Syndromes - etiology ; Neurotoxicity Syndromes - prevention & control ; Oxidative stress ; Stroke</subject><ispartof>Biochemical and biophysical research communications, 2009-08, Vol.386 (2), p.322-326</ispartof><rights>2009 Elsevier Inc.</rights><rights>2009 Elsevier Inc. All rights reserved 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-3f5b837d53780f780fabed9e703b4a339b6d250e62d2df94675d2fed2a2a66f63</citedby><cites>FETCH-LOGICAL-c484t-3f5b837d53780f780fabed9e703b4a339b6d250e62d2df94675d2fed2a2a66f63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2009.06.026$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19523448$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen-Roetling, Jing</creatorcontrib><creatorcontrib>Chen, Lifen</creatorcontrib><creatorcontrib>Regan, Raymond F.</creatorcontrib><title>Minocycline attenuates iron neurotoxicity in cortical cell cultures</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Iron neurotoxicity may contribute to the pathogenesis of intracerebral hemorrhage (ICH). The tetracycline derivative minocycline is protective in ICH models, due putatively to inhibition of microglial activation. Although minocycline also chelates iron, its effect on iron neurotoxicity has not been reported, and was examined in this study. Cortical cultures treated with 10
μM ferrous sulfate for 24
h sustained loss of most neurons and an increase in malondialdehyde. Minocycline prevented this injury, with near-complete protection at 30
μM. Two other inhibitors of microglial activation, doxycycline and macrophage/microglia inhibitory factor, were ineffective. Oxidation of isolated culture membranes by iron was also inhibited by minocycline. Consistent with prior observations, minocycline chelated iron in a siderophore colorometric assay; at concentrations less than 100
μM, its activity exceeded that of deferoxamine. These results suggest that attenuation of iron neurotoxicity may contribute to the beneficial effect of minocycline in hemorrhagic stroke and other CNS injury models.</description><subject>Animals</subject><subject>Cell culture</subject><subject>Cerebral Cortex - cytology</subject><subject>Cerebral Cortex - drug effects</subject><subject>Cerebral Hemorrhage - complications</subject><subject>Cytoprotection</subject><subject>Deferoxamine - pharmacology</subject><subject>Free radical</subject><subject>Hemoglobin toxicity</subject><subject>Inflammation</subject><subject>Intracerebral hemorrhage</subject><subject>Iron - toxicity</subject><subject>Iron Chelating Agents - pharmacology</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>Minocycline - pharmacology</subject><subject>Mouse</subject><subject>Neurons - drug effects</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neurotoxicity Syndromes - etiology</subject><subject>Neurotoxicity Syndromes - prevention & control</subject><subject>Oxidative stress</subject><subject>Stroke</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE2P1DAMhiMEYoeFP8AB9cStxXHTtJEQEhrxJS3iAhK3KE1cyKiTLEm6Yv49rWbEx4WD7YNfv7Yfxp5yaDhw-eLQjGOyDQKoBmQDKO-xHQcFNXIQ99kOAGSNin-9Yo9yPgBwLqR6yK646rAVYtix_Ucfoj3Z2QeqTCkUFlMoVz7FUAVaUizxp7e-nCofKhtT8dbMlaV5TctclkT5MXswmTnTk0u9Zl_evvm8f1_ffHr3Yf_6prZiEKVup24c2t51bT_AtIUZySnqoR2FaVs1SocdkESHblJC9p3DiRwaNFJOsr1mr86-t8t4JGcplGRmfZv80aSTjsbrfzvBf9ff4p3GfkAlxGrw_GKQ4o-FctFHn7dXTKC4ZI3AARBxFeJZaFPMOdH0ewkHvbHXB72x1xt7DVKv7NehZ3-f92fkAnsVvDwLaIV05ynpbD0FS84nskW76P_n_wskfZfg</recordid><startdate>20090821</startdate><enddate>20090821</enddate><creator>Chen-Roetling, Jing</creator><creator>Chen, Lifen</creator><creator>Regan, Raymond F.</creator><general>Elsevier Inc</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>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20090821</creationdate><title>Minocycline attenuates iron neurotoxicity in cortical cell cultures</title><author>Chen-Roetling, Jing ; Chen, Lifen ; Regan, Raymond F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c484t-3f5b837d53780f780fabed9e703b4a339b6d250e62d2df94675d2fed2a2a66f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Cell culture</topic><topic>Cerebral Cortex - cytology</topic><topic>Cerebral Cortex - drug effects</topic><topic>Cerebral Hemorrhage - complications</topic><topic>Cytoprotection</topic><topic>Deferoxamine - pharmacology</topic><topic>Free radical</topic><topic>Hemoglobin toxicity</topic><topic>Inflammation</topic><topic>Intracerebral hemorrhage</topic><topic>Iron - toxicity</topic><topic>Iron Chelating Agents - pharmacology</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>Minocycline - pharmacology</topic><topic>Mouse</topic><topic>Neurons - drug effects</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neurotoxicity Syndromes - etiology</topic><topic>Neurotoxicity Syndromes - prevention & control</topic><topic>Oxidative stress</topic><topic>Stroke</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen-Roetling, Jing</creatorcontrib><creatorcontrib>Chen, Lifen</creatorcontrib><creatorcontrib>Regan, Raymond F.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen-Roetling, Jing</au><au>Chen, Lifen</au><au>Regan, Raymond F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Minocycline attenuates iron neurotoxicity in cortical cell cultures</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2009-08-21</date><risdate>2009</risdate><volume>386</volume><issue>2</issue><spage>322</spage><epage>326</epage><pages>322-326</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Iron neurotoxicity may contribute to the pathogenesis of intracerebral hemorrhage (ICH). The tetracycline derivative minocycline is protective in ICH models, due putatively to inhibition of microglial activation. Although minocycline also chelates iron, its effect on iron neurotoxicity has not been reported, and was examined in this study. Cortical cultures treated with 10
μM ferrous sulfate for 24
h sustained loss of most neurons and an increase in malondialdehyde. Minocycline prevented this injury, with near-complete protection at 30
μM. Two other inhibitors of microglial activation, doxycycline and macrophage/microglia inhibitory factor, were ineffective. Oxidation of isolated culture membranes by iron was also inhibited by minocycline. Consistent with prior observations, minocycline chelated iron in a siderophore colorometric assay; at concentrations less than 100
μM, its activity exceeded that of deferoxamine. These results suggest that attenuation of iron neurotoxicity may contribute to the beneficial effect of minocycline in hemorrhagic stroke and other CNS injury models.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>19523448</pmid><doi>10.1016/j.bbrc.2009.06.026</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Animals Cell culture Cerebral Cortex - cytology Cerebral Cortex - drug effects Cerebral Hemorrhage - complications Cytoprotection Deferoxamine - pharmacology Free radical Hemoglobin toxicity Inflammation Intracerebral hemorrhage Iron - toxicity Iron Chelating Agents - pharmacology Mice Mice, Inbred Strains Minocycline - pharmacology Mouse Neurons - drug effects Neuroprotective Agents - pharmacology Neurotoxicity Syndromes - etiology Neurotoxicity Syndromes - prevention & control Oxidative stress Stroke |
| title | Minocycline attenuates iron neurotoxicity in cortical cell cultures |
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