E-4-hydroxy-2-nonenal is cytotoxic and cross-links cytoskeletal proteins in P19 neuroglial cultures
Lipid peroxidation increases with age in brain and is elevated further in Alzheimer's disease. E-4-hydroxy-2-nonenal and malondialdehyde are products of lipid peroxidation that can adduct and cross-link protein. Neurofibrillary tangles, a feature of Alzheimer's disease composed mostly of t...
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| Veröffentlicht in: | The American journal of pathology 1996-01, Vol.148 (1), p.89-93 |
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| container_title | The American journal of pathology |
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| creator | Montine, TJ Amarnath, V Martin, ME Strittmatter, WJ Graham, DG |
| description | Lipid peroxidation increases with age in brain and is elevated further in Alzheimer's disease. E-4-hydroxy-2-nonenal and malondialdehyde are products of lipid peroxidation that can adduct and cross-link protein. Neurofibrillary tangles, a feature of Alzheimer's disease composed mostly of tau protein, contain cross-linked and ubiquitin-conjugated protein. In P19 neuroglial cultures, E-4-hydroxy-2-nonenal was a potent cytotoxin that cross-linked cytoskeletal proteins, including tau into high molecular weight species that were conjugated with ubiquitin. Malondialdehyde formed monoadducts with cell protein but did not cross-link and was not cytotoxic. A non-crosslinking analogue of E-4-hydroxy-2-nonenal was not cytotoxic. E-4-Hydroxy-2-nonenal may contribute to neurodegeneration and neurofibrillary tangle formation in Alzheimer's disease. |
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E-4-hydroxy-2-nonenal and malondialdehyde are products of lipid peroxidation that can adduct and cross-link protein. Neurofibrillary tangles, a feature of Alzheimer's disease composed mostly of tau protein, contain cross-linked and ubiquitin-conjugated protein. In P19 neuroglial cultures, E-4-hydroxy-2-nonenal was a potent cytotoxin that cross-linked cytoskeletal proteins, including tau into high molecular weight species that were conjugated with ubiquitin. Malondialdehyde formed monoadducts with cell protein but did not cross-link and was not cytotoxic. A non-crosslinking analogue of E-4-hydroxy-2-nonenal was not cytotoxic. E-4-Hydroxy-2-nonenal may contribute to neurodegeneration and neurofibrillary tangle formation in Alzheimer's disease.</description><identifier>ISSN: 0002-9440</identifier><identifier>EISSN: 1525-2191</identifier><identifier>PMID: 8546230</identifier><identifier>CODEN: AJPAA4</identifier><language>eng</language><publisher>Bethesda, MD: ASIP</publisher><subject>3,4-Methylenedioxyamphetamine - chemistry ; 3,4-Methylenedioxyamphetamine - pharmacology ; Aldehydes - chemistry ; Aldehydes - pharmacology ; Biological and medical sciences ; Carcinoma, Embryonal ; Cytoskeletal Proteins - drug effects ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Lipid Peroxidation ; Medical sciences ; Neuroglia - chemistry ; Neuroglia - drug effects ; Neurology ; tau Proteins - chemistry ; Tumor Cells, Cultured</subject><ispartof>The American journal of pathology, 1996-01, Vol.148 (1), p.89-93</ispartof><rights>1996 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1861611/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1861611/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,4010,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3004543$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8546230$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Montine, TJ</creatorcontrib><creatorcontrib>Amarnath, V</creatorcontrib><creatorcontrib>Martin, ME</creatorcontrib><creatorcontrib>Strittmatter, WJ</creatorcontrib><creatorcontrib>Graham, DG</creatorcontrib><title>E-4-hydroxy-2-nonenal is cytotoxic and cross-links cytoskeletal proteins in P19 neuroglial cultures</title><title>The American journal of pathology</title><addtitle>Am J Pathol</addtitle><description>Lipid peroxidation increases with age in brain and is elevated further in Alzheimer's disease. E-4-hydroxy-2-nonenal and malondialdehyde are products of lipid peroxidation that can adduct and cross-link protein. Neurofibrillary tangles, a feature of Alzheimer's disease composed mostly of tau protein, contain cross-linked and ubiquitin-conjugated protein. In P19 neuroglial cultures, E-4-hydroxy-2-nonenal was a potent cytotoxin that cross-linked cytoskeletal proteins, including tau into high molecular weight species that were conjugated with ubiquitin. Malondialdehyde formed monoadducts with cell protein but did not cross-link and was not cytotoxic. A non-crosslinking analogue of E-4-hydroxy-2-nonenal was not cytotoxic. E-4-Hydroxy-2-nonenal may contribute to neurodegeneration and neurofibrillary tangle formation in Alzheimer's disease.</description><subject>3,4-Methylenedioxyamphetamine - chemistry</subject><subject>3,4-Methylenedioxyamphetamine - pharmacology</subject><subject>Aldehydes - chemistry</subject><subject>Aldehydes - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Embryonal</subject><subject>Cytoskeletal Proteins - drug effects</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Lipid Peroxidation</subject><subject>Medical sciences</subject><subject>Neuroglia - chemistry</subject><subject>Neuroglia - drug effects</subject><subject>Neurology</subject><subject>tau Proteins - chemistry</subject><subject>Tumor Cells, Cultured</subject><issn>0002-9440</issn><issn>1525-2191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE1LHEEQQIeQoKvmJwhzSHJr6O-PixBEk4CgB3Nuanp6dlp7u9fuGXX_vQO7iJ6K4j1eQX1pVkRQgSgx5GuzwhhTZDjHx81JrQ_LKpnGR82RFlxShleNu0Icjbu-5Ncdoijl5BPENtTW7aY85dfgWkh960quFcWQHvekPvrop8Xcljz5kGobUntHTJv8XPI6hgW5OU5z8fWs-TZArP77YZ42_6-v7i__opvbP_8uf9-gkVE8Iccodz0YpgUbpFZCCtUR6DpN-6GTCoP3xqgOe6UFYEl6IpVnahDa8KEDdtpc7Lvbudv43vk0FYh2W8IGys5mCPYzSWG06_xsiZZEErIEfh0CJT_Nvk52E6rzMULyea5WKUOZwXgRzz9eej9xeOvCfxw4VAdxKJBcqO8aw5gLzhbt514bw3p8CcXbuoEYlyix8LAlXFtitWFv5f-Qaw</recordid><startdate>19960101</startdate><enddate>19960101</enddate><creator>Montine, TJ</creator><creator>Amarnath, V</creator><creator>Martin, ME</creator><creator>Strittmatter, WJ</creator><creator>Graham, DG</creator><general>ASIP</general><general>American Society for Investigative Pathology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19960101</creationdate><title>E-4-hydroxy-2-nonenal is cytotoxic and cross-links cytoskeletal proteins in P19 neuroglial cultures</title><author>Montine, TJ ; Amarnath, V ; Martin, ME ; Strittmatter, WJ ; Graham, DG</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h320t-c324cda93853f6875657b1abb82dfb670aee997b0e785a061d167e37f5894fba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>3,4-Methylenedioxyamphetamine - chemistry</topic><topic>3,4-Methylenedioxyamphetamine - pharmacology</topic><topic>Aldehydes - chemistry</topic><topic>Aldehydes - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Embryonal</topic><topic>Cytoskeletal Proteins - drug effects</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Lipid Peroxidation</topic><topic>Medical sciences</topic><topic>Neuroglia - chemistry</topic><topic>Neuroglia - drug effects</topic><topic>Neurology</topic><topic>tau Proteins - chemistry</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Montine, TJ</creatorcontrib><creatorcontrib>Amarnath, V</creatorcontrib><creatorcontrib>Martin, ME</creatorcontrib><creatorcontrib>Strittmatter, WJ</creatorcontrib><creatorcontrib>Graham, DG</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The American journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Montine, TJ</au><au>Amarnath, V</au><au>Martin, ME</au><au>Strittmatter, WJ</au><au>Graham, DG</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>E-4-hydroxy-2-nonenal is cytotoxic and cross-links cytoskeletal proteins in P19 neuroglial cultures</atitle><jtitle>The American journal of pathology</jtitle><addtitle>Am J Pathol</addtitle><date>1996-01-01</date><risdate>1996</risdate><volume>148</volume><issue>1</issue><spage>89</spage><epage>93</epage><pages>89-93</pages><issn>0002-9440</issn><eissn>1525-2191</eissn><coden>AJPAA4</coden><abstract>Lipid peroxidation increases with age in brain and is elevated further in Alzheimer's disease. E-4-hydroxy-2-nonenal and malondialdehyde are products of lipid peroxidation that can adduct and cross-link protein. Neurofibrillary tangles, a feature of Alzheimer's disease composed mostly of tau protein, contain cross-linked and ubiquitin-conjugated protein. In P19 neuroglial cultures, E-4-hydroxy-2-nonenal was a potent cytotoxin that cross-linked cytoskeletal proteins, including tau into high molecular weight species that were conjugated with ubiquitin. Malondialdehyde formed monoadducts with cell protein but did not cross-link and was not cytotoxic. A non-crosslinking analogue of E-4-hydroxy-2-nonenal was not cytotoxic. E-4-Hydroxy-2-nonenal may contribute to neurodegeneration and neurofibrillary tangle formation in Alzheimer's disease.</abstract><cop>Bethesda, MD</cop><pub>ASIP</pub><pmid>8546230</pmid><tpages>5</tpages></addata></record> |
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| ispartof | The American journal of pathology, 1996-01, Vol.148 (1), p.89-93 |
| issn | 0002-9440 1525-2191 |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | 3,4-Methylenedioxyamphetamine - chemistry 3,4-Methylenedioxyamphetamine - pharmacology Aldehydes - chemistry Aldehydes - pharmacology Biological and medical sciences Carcinoma, Embryonal Cytoskeletal Proteins - drug effects Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Lipid Peroxidation Medical sciences Neuroglia - chemistry Neuroglia - drug effects Neurology tau Proteins - chemistry Tumor Cells, Cultured |
| title | E-4-hydroxy-2-nonenal is cytotoxic and cross-links cytoskeletal proteins in P19 neuroglial cultures |
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