Calcium/calmodulin-dependent protein kinase II containing a nuclear localizing signal is altered in retinal neurons exposed to N-methyl- d-aspartate

This study investigated N-methyl- d-aspartate (NMDA) mediated cell death and its possible regulation by calcium/calmodulin-dependent protein kinase II (CaMKII) in the adult rat retina. To investigate cell death, the terminal deoxyribonucleotidyltransferase (TdT)-mediated biotin-16-dUTP nick-end labe...

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Veröffentlicht in:Brain research. Molecular brain research. 2000-03, Vol.76 (2), p.253-265
Hauptverfasser: Laabich, Aicha, Li, Guangyu, Cooper, Nigel G.F
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container_title Brain research. Molecular brain research.
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creator Laabich, Aicha
Li, Guangyu
Cooper, Nigel G.F
description This study investigated N-methyl- d-aspartate (NMDA) mediated cell death and its possible regulation by calcium/calmodulin-dependent protein kinase II (CaMKII) in the adult rat retina. To investigate cell death, the terminal deoxyribonucleotidyltransferase (TdT)-mediated biotin-16-dUTP nick-end labelling (TUNEL) method was used to detect fragmented DNA in fixed tissue sections of rat retina. The TUNEL assay confirmed that apoptosis occurs in the inner nuclear layer (INL) and ganglion cell layer (GCL) following NMDA injection. The level of antibody binding to CaMKII-α, the activity of CaMKII, and the mRNA level for the α B subunit of CaMKII were found to be elevated for short time periods (30 min, 2 h) after a single intravitreal injection of NMDA. In contrast to this, there was a decrease in CaMKII activity and in the CaMKII-α B mRNA levels at longer time periods (24 h) following injection of NMDA. These effects were specific for the mRNA for the α B subunit, an alternatively spliced product of the CaMKII-α gene, that contains a nuclear localizing signal (NLS) known to target this protein to the nucleus. It is suggested that regulated expression of CaMKII-α B could be involved in the NMDA-mediated cell death in retinal neurons.
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To investigate cell death, the terminal deoxyribonucleotidyltransferase (TdT)-mediated biotin-16-dUTP nick-end labelling (TUNEL) method was used to detect fragmented DNA in fixed tissue sections of rat retina. The TUNEL assay confirmed that apoptosis occurs in the inner nuclear layer (INL) and ganglion cell layer (GCL) following NMDA injection. The level of antibody binding to CaMKII-α, the activity of CaMKII, and the mRNA level for the α B subunit of CaMKII were found to be elevated for short time periods (30 min, 2 h) after a single intravitreal injection of NMDA. In contrast to this, there was a decrease in CaMKII activity and in the CaMKII-α B mRNA levels at longer time periods (24 h) following injection of NMDA. These effects were specific for the mRNA for the α B subunit, an alternatively spliced product of the CaMKII-α gene, that contains a nuclear localizing signal (NLS) known to target this protein to the nucleus. 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Psychology ; In Situ Nick-End Labeling ; Kinetics ; N-Methyl-D-aspartic acid ; N-Methylaspartate - pharmacology ; Neurons - drug effects ; Neurons - enzymology ; NMDA ; nuclear localization signal ; Nucleus ; Polymerase Chain Reaction ; Rat retina ; Rats ; Rats, Sprague-Dawley ; Retina - cytology ; Retina - enzymology ; Transcription, Genetic - drug effects ; Vertebrates: nervous system and sense organs</subject><ispartof>Brain research. 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Molecular brain research.</title><addtitle>Brain Res Mol Brain Res</addtitle><description>This study investigated N-methyl- d-aspartate (NMDA) mediated cell death and its possible regulation by calcium/calmodulin-dependent protein kinase II (CaMKII) in the adult rat retina. To investigate cell death, the terminal deoxyribonucleotidyltransferase (TdT)-mediated biotin-16-dUTP nick-end labelling (TUNEL) method was used to detect fragmented DNA in fixed tissue sections of rat retina. The TUNEL assay confirmed that apoptosis occurs in the inner nuclear layer (INL) and ganglion cell layer (GCL) following NMDA injection. The level of antibody binding to CaMKII-α, the activity of CaMKII, and the mRNA level for the α B subunit of CaMKII were found to be elevated for short time periods (30 min, 2 h) after a single intravitreal injection of NMDA. In contrast to this, there was a decrease in CaMKII activity and in the CaMKII-α B mRNA levels at longer time periods (24 h) following injection of NMDA. These effects were specific for the mRNA for the α B subunit, an alternatively spliced product of the CaMKII-α gene, that contains a nuclear localizing signal (NLS) known to target this protein to the nucleus. It is suggested that regulated expression of CaMKII-α B could be involved in the NMDA-mediated cell death in retinal neurons.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Type 2</subject><subject>Calcium-Calmodulin-Dependent Protein Kinases - chemistry</subject><subject>Calcium-Calmodulin-Dependent Protein Kinases - genetics</subject><subject>Calcium-Calmodulin-Dependent Protein Kinases - metabolism</subject><subject>CaMKII-α</subject><subject>CaMKII-α B</subject><subject>Cell Death</subject><subject>Dizocilpine Maleate - pharmacology</subject><subject>Eye and associated structures. Visual pathways and centers. Vision</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>In Situ Nick-End Labeling</subject><subject>Kinetics</subject><subject>N-Methyl-D-aspartic acid</subject><subject>N-Methylaspartate - pharmacology</subject><subject>Neurons - drug effects</subject><subject>Neurons - enzymology</subject><subject>NMDA</subject><subject>nuclear localization signal</subject><subject>Nucleus</subject><subject>Polymerase Chain Reaction</subject><subject>Rat retina</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Retina - cytology</subject><subject>Retina - enzymology</subject><subject>Transcription, Genetic - drug effects</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0169-328X</issn><issn>1872-6941</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc-O1SAUxhujce6MPoKGhTHjAgdaWtqVMTf-uclEF2rijpzC6YhSuAI1js_hA0vn3qi7YQHJ4fcdDt9XVY84e84Z7y4-lG2gTd1_PmfsGSuro_xOteG9rGk3CH632vxFTqrTlL4Whvec369OOJNdLRnbVL-34LRd5gsNbg5mcdZTg3v0Bn0m-xgyWk--WQ8JyW5HdPAZrLf-igDxi3YIkbhQ1PbXWkz2yoMjNhFwGSMaUuQRs12rHpcYfCL4cx9SucqBvKMz5i_XjhJDIe0hZsj4oLo3gUv48HieVZ9ev_q4fUsv37_ZbV9eUi1qnqkUoIdO4yShFiOITg71NHLZN81Qg5ajnkRtWj6OfKi56LvRoARdt6MwiJNuzqqnh77ln98XTFnNNml0DjyGJSlZfOJDJ28FuWwH0QhewPYA6hhSijipfbQzxGvFmVpzUze5qTUUxZi6yU2tusfHB5ZxRvOf6hBUAZ4cAUjF7CmC1zb945pGtnId9MUBw2LbD4tRJW3RazQ2os7KBHvLJH8AYM-39A</recordid><startdate>20000329</startdate><enddate>20000329</enddate><creator>Laabich, Aicha</creator><creator>Li, Guangyu</creator><creator>Cooper, Nigel G.F</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><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>7QP</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>20000329</creationdate><title>Calcium/calmodulin-dependent protein kinase II containing a nuclear localizing signal is altered in retinal neurons exposed to N-methyl- d-aspartate</title><author>Laabich, Aicha ; Li, Guangyu ; Cooper, Nigel G.F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-74ac96cef7a24ba46792fb1783392ac7bcf42d51bb1921486bde7ac25b4deefc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Calcium-Calmodulin-Dependent Protein Kinase Type 2</topic><topic>Calcium-Calmodulin-Dependent Protein Kinases - chemistry</topic><topic>Calcium-Calmodulin-Dependent Protein Kinases - genetics</topic><topic>Calcium-Calmodulin-Dependent Protein Kinases - metabolism</topic><topic>CaMKII-α</topic><topic>CaMKII-α B</topic><topic>Cell Death</topic><topic>Dizocilpine Maleate - pharmacology</topic><topic>Eye and associated structures. Visual pathways and centers. Vision</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>In Situ Nick-End Labeling</topic><topic>Kinetics</topic><topic>N-Methyl-D-aspartic acid</topic><topic>N-Methylaspartate - pharmacology</topic><topic>Neurons - drug effects</topic><topic>Neurons - enzymology</topic><topic>NMDA</topic><topic>nuclear localization signal</topic><topic>Nucleus</topic><topic>Polymerase Chain Reaction</topic><topic>Rat retina</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Retina - cytology</topic><topic>Retina - enzymology</topic><topic>Transcription, Genetic - drug effects</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Laabich, Aicha</creatorcontrib><creatorcontrib>Li, Guangyu</creatorcontrib><creatorcontrib>Cooper, Nigel G.F</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Brain research. Molecular brain research.</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Laabich, Aicha</au><au>Li, Guangyu</au><au>Cooper, Nigel G.F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Calcium/calmodulin-dependent protein kinase II containing a nuclear localizing signal is altered in retinal neurons exposed to N-methyl- d-aspartate</atitle><jtitle>Brain research. Molecular brain research.</jtitle><addtitle>Brain Res Mol Brain Res</addtitle><date>2000-03-29</date><risdate>2000</risdate><volume>76</volume><issue>2</issue><spage>253</spage><epage>265</epage><pages>253-265</pages><issn>0169-328X</issn><eissn>1872-6941</eissn><abstract>This study investigated N-methyl- d-aspartate (NMDA) mediated cell death and its possible regulation by calcium/calmodulin-dependent protein kinase II (CaMKII) in the adult rat retina. 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It is suggested that regulated expression of CaMKII-α B could be involved in the NMDA-mediated cell death in retinal neurons.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>10762700</pmid><doi>10.1016/S0169-328X(00)00006-1</doi><tpages>13</tpages></addata></record>
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ispartof Brain research. Molecular brain research., 2000-03, Vol.76 (2), p.253-265
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subjects Animals
Apoptosis
Biological and medical sciences
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases - chemistry
Calcium-Calmodulin-Dependent Protein Kinases - genetics
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
CaMKII-α
CaMKII-α B
Cell Death
Dizocilpine Maleate - pharmacology
Eye and associated structures. Visual pathways and centers. Vision
Fundamental and applied biological sciences. Psychology
In Situ Nick-End Labeling
Kinetics
N-Methyl-D-aspartic acid
N-Methylaspartate - pharmacology
Neurons - drug effects
Neurons - enzymology
NMDA
nuclear localization signal
Nucleus
Polymerase Chain Reaction
Rat retina
Rats
Rats, Sprague-Dawley
Retina - cytology
Retina - enzymology
Transcription, Genetic - drug effects
Vertebrates: nervous system and sense organs
title Calcium/calmodulin-dependent protein kinase II containing a nuclear localizing signal is altered in retinal neurons exposed to N-methyl- d-aspartate
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