Matrix Metalloproteinases 2 and 9 Fail to Influence Drug-Induced Neuroapoptosis in Developing Rat Brain
Matrix metalloproteinases (MMPs) play an essential role in tissue repair, cell death, and morphogenesis. The aim of the present study was to investigate potential involvement of selected MMPs in the pathogenesis of neuronal apoptosis induced by the NMDA antagonist MK-801 (dizocilpine) or the GABA A...
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Veröffentlicht in: | Neurotoxicity research 2011-05, Vol.19 (4), p.638-648 |
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creator | Uckermann, Ortrud Luksch, Hella Stefovska, Vanya Hoehna, Yvonne Marzahn, Jenny Theil, Marlen Pesic, Mila Górkiewicz, Tomasz Gawlak, Maciej Wilczynski, Grzegorz M. Kaczmarek, Leszek Ikonomidou, Chrysanthy |
description | Matrix metalloproteinases (MMPs) play an essential role in tissue repair, cell death, and morphogenesis. The aim of the present study was to investigate potential involvement of selected MMPs in the pathogenesis of neuronal apoptosis induced by the NMDA antagonist MK-801 (dizocilpine) or the GABA
A
agonist phenobarbital in infant rats, transgenic rats overexpressing MMP-9 and MMP-9 knockout mice. Seven-day-old rats or knockout mice received intraperitoneal injections of MK-801, 1 mg/kg, or phenobarbital, 50 mg/kg. At different survival intervals following administration of the compounds (1–72 h), pups were sacrificed, tissue from different brain regions was isolated, and the expression and activity of MMP-2 and MMP-9 were analyzed by real-time PCR, western blot, and zymography. In addition, brains were fixed and processed for TUNEL staining. In all the brain regions analyzed, we found an increased number of TUNEL-positive cells 24 h after administration of MK-801. After treatment, we detected no significant increase in MMP-2 or MMP-9 mRNA expression in cortical areas. No changes in the MMP-9 protein expression or gelatinolytic activity of MMP-2 were observed in conjunction with MK-801 or phenobarbital-induced neuroapoptosis in any brain region analyzed. The extent of neurodegeneration induced by MK-801 or phenobarbital was not altered in MMP-9 transgenic rats and was increased in MMP-9 knockout mice compared to wild-type rats and mice. Treatment with the panmetalloproteinase inhibitor GM6001 did not confer protection against MK-801-induced apoptotic cell death in the developing rat brain. Our results suggest that activation of MMP-9 and MMP-2 does not contribute to pathogenesis of neuronal apoptosis caused by NMDA antagonists or GABA
A
agonists in the developing rat and mouse brain. |
doi_str_mv | 10.1007/s12640-010-9211-1 |
format | Article |
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A
agonist phenobarbital in infant rats, transgenic rats overexpressing MMP-9 and MMP-9 knockout mice. Seven-day-old rats or knockout mice received intraperitoneal injections of MK-801, 1 mg/kg, or phenobarbital, 50 mg/kg. At different survival intervals following administration of the compounds (1–72 h), pups were sacrificed, tissue from different brain regions was isolated, and the expression and activity of MMP-2 and MMP-9 were analyzed by real-time PCR, western blot, and zymography. In addition, brains were fixed and processed for TUNEL staining. In all the brain regions analyzed, we found an increased number of TUNEL-positive cells 24 h after administration of MK-801. After treatment, we detected no significant increase in MMP-2 or MMP-9 mRNA expression in cortical areas. No changes in the MMP-9 protein expression or gelatinolytic activity of MMP-2 were observed in conjunction with MK-801 or phenobarbital-induced neuroapoptosis in any brain region analyzed. The extent of neurodegeneration induced by MK-801 or phenobarbital was not altered in MMP-9 transgenic rats and was increased in MMP-9 knockout mice compared to wild-type rats and mice. Treatment with the panmetalloproteinase inhibitor GM6001 did not confer protection against MK-801-induced apoptotic cell death in the developing rat brain. Our results suggest that activation of MMP-9 and MMP-2 does not contribute to pathogenesis of neuronal apoptosis caused by NMDA antagonists or GABA
A
agonists in the developing rat and mouse brain.</description><identifier>ISSN: 1029-8428</identifier><identifier>EISSN: 1476-3524</identifier><identifier>DOI: 10.1007/s12640-010-9211-1</identifier><identifier>PMID: 20661683</identifier><language>eng</language><publisher>New York: Springer-Verlag</publisher><subject>Animals ; Animals, Newborn ; Apoptosis - drug effects ; Apoptosis - physiology ; Biomedical and Life Sciences ; Biomedicine ; Brain - drug effects ; Brain - enzymology ; Brain - growth & development ; Cell Biology ; Dizocilpine Maleate - toxicity ; Matrix Metalloproteinase 2 - metabolism ; Matrix Metalloproteinase 2 - physiology ; Matrix Metalloproteinase 9 - metabolism ; Matrix Metalloproteinase 9 - physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurobiology ; Neurochemistry ; Neurology ; Neurons - cytology ; Neurons - drug effects ; Neurons - enzymology ; Neurosciences ; Pharmacology/Toxicology ; Phenobarbital - toxicity ; Rats ; Rats, Wistar</subject><ispartof>Neurotoxicity research, 2011-05, Vol.19 (4), p.638-648</ispartof><rights>Springer Science+Business Media, LLC 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-9bc1877864b0f338701497e84211bde767b14ced86d096202424c53125b335973</citedby><cites>FETCH-LOGICAL-c375t-9bc1877864b0f338701497e84211bde767b14ced86d096202424c53125b335973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12640-010-9211-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12640-010-9211-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20661683$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Uckermann, Ortrud</creatorcontrib><creatorcontrib>Luksch, Hella</creatorcontrib><creatorcontrib>Stefovska, Vanya</creatorcontrib><creatorcontrib>Hoehna, Yvonne</creatorcontrib><creatorcontrib>Marzahn, Jenny</creatorcontrib><creatorcontrib>Theil, Marlen</creatorcontrib><creatorcontrib>Pesic, Mila</creatorcontrib><creatorcontrib>Górkiewicz, Tomasz</creatorcontrib><creatorcontrib>Gawlak, Maciej</creatorcontrib><creatorcontrib>Wilczynski, Grzegorz M.</creatorcontrib><creatorcontrib>Kaczmarek, Leszek</creatorcontrib><creatorcontrib>Ikonomidou, Chrysanthy</creatorcontrib><title>Matrix Metalloproteinases 2 and 9 Fail to Influence Drug-Induced Neuroapoptosis in Developing Rat Brain</title><title>Neurotoxicity research</title><addtitle>Neurotox Res</addtitle><addtitle>Neurotox Res</addtitle><description>Matrix metalloproteinases (MMPs) play an essential role in tissue repair, cell death, and morphogenesis. The aim of the present study was to investigate potential involvement of selected MMPs in the pathogenesis of neuronal apoptosis induced by the NMDA antagonist MK-801 (dizocilpine) or the GABA
A
agonist phenobarbital in infant rats, transgenic rats overexpressing MMP-9 and MMP-9 knockout mice. Seven-day-old rats or knockout mice received intraperitoneal injections of MK-801, 1 mg/kg, or phenobarbital, 50 mg/kg. At different survival intervals following administration of the compounds (1–72 h), pups were sacrificed, tissue from different brain regions was isolated, and the expression and activity of MMP-2 and MMP-9 were analyzed by real-time PCR, western blot, and zymography. In addition, brains were fixed and processed for TUNEL staining. In all the brain regions analyzed, we found an increased number of TUNEL-positive cells 24 h after administration of MK-801. After treatment, we detected no significant increase in MMP-2 or MMP-9 mRNA expression in cortical areas. No changes in the MMP-9 protein expression or gelatinolytic activity of MMP-2 were observed in conjunction with MK-801 or phenobarbital-induced neuroapoptosis in any brain region analyzed. The extent of neurodegeneration induced by MK-801 or phenobarbital was not altered in MMP-9 transgenic rats and was increased in MMP-9 knockout mice compared to wild-type rats and mice. Treatment with the panmetalloproteinase inhibitor GM6001 did not confer protection against MK-801-induced apoptotic cell death in the developing rat brain. Our results suggest that activation of MMP-9 and MMP-2 does not contribute to pathogenesis of neuronal apoptosis caused by NMDA antagonists or GABA
A
agonists in the developing rat and mouse brain.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain - drug effects</subject><subject>Brain - enzymology</subject><subject>Brain - growth & development</subject><subject>Cell Biology</subject><subject>Dizocilpine Maleate - toxicity</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 2 - physiology</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Matrix Metalloproteinase 9 - physiology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Neurobiology</subject><subject>Neurochemistry</subject><subject>Neurology</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - enzymology</subject><subject>Neurosciences</subject><subject>Pharmacology/Toxicology</subject><subject>Phenobarbital - toxicity</subject><subject>Rats</subject><subject>Rats, Wistar</subject><issn>1029-8428</issn><issn>1476-3524</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtvHCEQhJEVy8_8gFwibjlh08DAcEzsrL2SH5LlnBEz07vCmoUNzETOvw-rdXz0qVvqqmrVR8gX4BfAubksILTijANnVgAwOCAnoIxmshHqU925sKxVoj0mp6W8cC6g0eaIHAuuNehWnpD1vZ9yeKX3OPlxTNucJgzRFyxUUB8HaunCh5FOiS7japwx9kiv87xmyzjMPQ70Aeec_DZtp1RCoSHSa_yDNSrENX3yE_2RfYjn5HDlx4Kf3-YZ-bX4-Xx1y-4eb5ZX3-9YL00zMdv10BrTatXxlZSt4aCswdoBoBvQaNOBql9bPXCrBRdKqL6RIJpOysYaeUa-7XNrk98zlsltQulxHH3ENBdnuZDGSt1UJeyVfU6lZFy5bQ4bn_864G6H1-3xuorX7fA6qJ6vb-lzt8Hh3fGfZxWIvaDUU1xjdi9pzrE2_iD1H3lUg4E</recordid><startdate>20110501</startdate><enddate>20110501</enddate><creator>Uckermann, Ortrud</creator><creator>Luksch, Hella</creator><creator>Stefovska, Vanya</creator><creator>Hoehna, Yvonne</creator><creator>Marzahn, Jenny</creator><creator>Theil, Marlen</creator><creator>Pesic, Mila</creator><creator>Górkiewicz, Tomasz</creator><creator>Gawlak, Maciej</creator><creator>Wilczynski, Grzegorz M.</creator><creator>Kaczmarek, Leszek</creator><creator>Ikonomidou, Chrysanthy</creator><general>Springer-Verlag</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><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20110501</creationdate><title>Matrix Metalloproteinases 2 and 9 Fail to Influence Drug-Induced Neuroapoptosis in Developing Rat Brain</title><author>Uckermann, Ortrud ; Luksch, Hella ; Stefovska, Vanya ; Hoehna, Yvonne ; Marzahn, Jenny ; Theil, Marlen ; Pesic, Mila ; Górkiewicz, Tomasz ; Gawlak, Maciej ; Wilczynski, Grzegorz M. ; Kaczmarek, Leszek ; Ikonomidou, Chrysanthy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-9bc1877864b0f338701497e84211bde767b14ced86d096202424c53125b335973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - physiology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain - drug effects</topic><topic>Brain - enzymology</topic><topic>Brain - growth & development</topic><topic>Cell Biology</topic><topic>Dizocilpine Maleate - toxicity</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Matrix Metalloproteinase 2 - physiology</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>Matrix Metalloproteinase 9 - physiology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Neurobiology</topic><topic>Neurochemistry</topic><topic>Neurology</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neurons - enzymology</topic><topic>Neurosciences</topic><topic>Pharmacology/Toxicology</topic><topic>Phenobarbital - toxicity</topic><topic>Rats</topic><topic>Rats, Wistar</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Uckermann, Ortrud</creatorcontrib><creatorcontrib>Luksch, Hella</creatorcontrib><creatorcontrib>Stefovska, Vanya</creatorcontrib><creatorcontrib>Hoehna, Yvonne</creatorcontrib><creatorcontrib>Marzahn, Jenny</creatorcontrib><creatorcontrib>Theil, Marlen</creatorcontrib><creatorcontrib>Pesic, Mila</creatorcontrib><creatorcontrib>Górkiewicz, Tomasz</creatorcontrib><creatorcontrib>Gawlak, Maciej</creatorcontrib><creatorcontrib>Wilczynski, Grzegorz M.</creatorcontrib><creatorcontrib>Kaczmarek, Leszek</creatorcontrib><creatorcontrib>Ikonomidou, Chrysanthy</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><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Neurotoxicity research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Uckermann, Ortrud</au><au>Luksch, Hella</au><au>Stefovska, Vanya</au><au>Hoehna, Yvonne</au><au>Marzahn, Jenny</au><au>Theil, Marlen</au><au>Pesic, Mila</au><au>Górkiewicz, Tomasz</au><au>Gawlak, Maciej</au><au>Wilczynski, Grzegorz M.</au><au>Kaczmarek, Leszek</au><au>Ikonomidou, Chrysanthy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Matrix Metalloproteinases 2 and 9 Fail to Influence Drug-Induced Neuroapoptosis in Developing Rat Brain</atitle><jtitle>Neurotoxicity research</jtitle><stitle>Neurotox Res</stitle><addtitle>Neurotox Res</addtitle><date>2011-05-01</date><risdate>2011</risdate><volume>19</volume><issue>4</issue><spage>638</spage><epage>648</epage><pages>638-648</pages><issn>1029-8428</issn><eissn>1476-3524</eissn><abstract>Matrix metalloproteinases (MMPs) play an essential role in tissue repair, cell death, and morphogenesis. The aim of the present study was to investigate potential involvement of selected MMPs in the pathogenesis of neuronal apoptosis induced by the NMDA antagonist MK-801 (dizocilpine) or the GABA
A
agonist phenobarbital in infant rats, transgenic rats overexpressing MMP-9 and MMP-9 knockout mice. Seven-day-old rats or knockout mice received intraperitoneal injections of MK-801, 1 mg/kg, or phenobarbital, 50 mg/kg. At different survival intervals following administration of the compounds (1–72 h), pups were sacrificed, tissue from different brain regions was isolated, and the expression and activity of MMP-2 and MMP-9 were analyzed by real-time PCR, western blot, and zymography. In addition, brains were fixed and processed for TUNEL staining. In all the brain regions analyzed, we found an increased number of TUNEL-positive cells 24 h after administration of MK-801. After treatment, we detected no significant increase in MMP-2 or MMP-9 mRNA expression in cortical areas. No changes in the MMP-9 protein expression or gelatinolytic activity of MMP-2 were observed in conjunction with MK-801 or phenobarbital-induced neuroapoptosis in any brain region analyzed. The extent of neurodegeneration induced by MK-801 or phenobarbital was not altered in MMP-9 transgenic rats and was increased in MMP-9 knockout mice compared to wild-type rats and mice. Treatment with the panmetalloproteinase inhibitor GM6001 did not confer protection against MK-801-induced apoptotic cell death in the developing rat brain. Our results suggest that activation of MMP-9 and MMP-2 does not contribute to pathogenesis of neuronal apoptosis caused by NMDA antagonists or GABA
A
agonists in the developing rat and mouse brain.</abstract><cop>New York</cop><pub>Springer-Verlag</pub><pmid>20661683</pmid><doi>10.1007/s12640-010-9211-1</doi><tpages>11</tpages></addata></record> |
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subjects | Animals Animals, Newborn Apoptosis - drug effects Apoptosis - physiology Biomedical and Life Sciences Biomedicine Brain - drug effects Brain - enzymology Brain - growth & development Cell Biology Dizocilpine Maleate - toxicity Matrix Metalloproteinase 2 - metabolism Matrix Metalloproteinase 2 - physiology Matrix Metalloproteinase 9 - metabolism Matrix Metalloproteinase 9 - physiology Mice Mice, Inbred C57BL Mice, Knockout Neurobiology Neurochemistry Neurology Neurons - cytology Neurons - drug effects Neurons - enzymology Neurosciences Pharmacology/Toxicology Phenobarbital - toxicity Rats Rats, Wistar |
title | Matrix Metalloproteinases 2 and 9 Fail to Influence Drug-Induced Neuroapoptosis in Developing Rat Brain |
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