Diphtheria Toxin-induced Autophagic Cardiomyocyte Death Plays a Pathogenic Role in Mouse Model of Heart Failure
It is still not clear whether loss of cardiomyocytes through programmed cell death causes heart failure. To clarify the role of cell death in heart failure, we generated transgenic mice (TG) that express human diphtheria toxin receptor in the hearts. A mosaic expression pattern of the transgene was...
Gespeichert in:
| Veröffentlicht in: | The Journal of biological chemistry 2004-09, Vol.279 (39), p.41095-41103 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 41103 |
|---|---|
| container_issue | 39 |
| container_start_page | 41095 |
| container_title | The Journal of biological chemistry |
| container_volume | 279 |
| creator | Akazawa, Hiroshi Komazaki, Shinji Shimomura, Hiroaki Terasaki, Fumio Zou, Yunzeng Takano, Hiroyuki Nagai, Toshio Komuro, Issei |
| description | It is still not clear whether loss of cardiomyocytes through programmed cell death causes heart failure. To clarify the role of cell death in heart failure, we generated transgenic mice (TG) that express human diphtheria toxin receptor in the hearts. A mosaic expression pattern of the transgene was observed, and the transgene-expressing cardiomyocytes (17.3% of the total cardiomyocytes) were diffusely scattered throughout the ventricles. Intramuscular injection of diphtheria toxin induced complete elimination of the transgene-expressing cardiomyocytes within 7 days, and ∼80% of TG showed pathophysiological features characteristic of heart failure and were dead within 14 days. Degenerated cardiomyocytes of the TG heart showed characteristic features indicative of autophagic cell death such as up-regulated lysosomal markers and abundant autophagosomes containing cytosolic organelles like cardiomyocytes of human dilated cardiomyopathy. The heart failure-inducible TG are a useful model for dilated cardiomyopathy, and provided evidence indicating that myocardial cell loss through autophagic cell death plays of a causal role in the pathogenesis heart failure. |
| doi_str_mv | 10.1074/jbc.M313084200 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_21384814</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S002192582077208X</els_id><sourcerecordid>21384814</sourcerecordid><originalsourceid>FETCH-LOGICAL-c506t-d0dcf5dc102103c2c1bc75bd1d3851817717205c4bbd1f7df94f237e54095df13</originalsourceid><addsrcrecordid>eNp1kEFv1DAQRi1ERZfClSPyAXHL1mPHJDlW25YitWpVFYmb5diTjaskXuwE2H_PoF2pJ3ywNdab0TePsQ8g1iCq8vy5des7BUrUpRTiFVuBqFWhNPx4zVZCSCgaqetT9jbnZ0GnbOANOwUtK8LlisXLsOvnHlOw_Cn-CVMRJr849PximeOut9vg-MYmH-K4j24_I79EO_f8YbD7zC1_oCJucSLsMQ7Iw8Tv4pKRbo8Djx2_QZtmfm3DsCR8x046O2R8f3zP2Pfrq6fNTXF7__Xb5uK2cFp8mQsvvOu0d0AbCOWkg9ZVuvXgVa2hhqoCWkC7sqW_rvJdU3ZSVahL0WjfgTpjnw9zdyn-XDDPZgzZ4TDYCSmekaDqsoaSwPUBdCnmnLAzuxRGm_YGhPmn2JBi86KYGj4eJy_tiP4FPzol4NMB6MO2_x0SmjZE1-NoZNUY1ZgSKCRh9QFD0vArYDLZBZxIPbW42fgY_hfhLwqklfM</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>21384814</pqid></control><display><type>article</type><title>Diphtheria Toxin-induced Autophagic Cardiomyocyte Death Plays a Pathogenic Role in Mouse Model of Heart Failure</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Akazawa, Hiroshi ; Komazaki, Shinji ; Shimomura, Hiroaki ; Terasaki, Fumio ; Zou, Yunzeng ; Takano, Hiroyuki ; Nagai, Toshio ; Komuro, Issei</creator><creatorcontrib>Akazawa, Hiroshi ; Komazaki, Shinji ; Shimomura, Hiroaki ; Terasaki, Fumio ; Zou, Yunzeng ; Takano, Hiroyuki ; Nagai, Toshio ; Komuro, Issei</creatorcontrib><description>It is still not clear whether loss of cardiomyocytes through programmed cell death causes heart failure. To clarify the role of cell death in heart failure, we generated transgenic mice (TG) that express human diphtheria toxin receptor in the hearts. A mosaic expression pattern of the transgene was observed, and the transgene-expressing cardiomyocytes (17.3% of the total cardiomyocytes) were diffusely scattered throughout the ventricles. Intramuscular injection of diphtheria toxin induced complete elimination of the transgene-expressing cardiomyocytes within 7 days, and ∼80% of TG showed pathophysiological features characteristic of heart failure and were dead within 14 days. Degenerated cardiomyocytes of the TG heart showed characteristic features indicative of autophagic cell death such as up-regulated lysosomal markers and abundant autophagosomes containing cytosolic organelles like cardiomyocytes of human dilated cardiomyopathy. The heart failure-inducible TG are a useful model for dilated cardiomyopathy, and provided evidence indicating that myocardial cell loss through autophagic cell death plays of a causal role in the pathogenesis heart failure.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M313084200</identifier><identifier>PMID: 15272002</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Autophagy ; Blotting, Northern ; Blotting, Western ; Cell Death ; Cytosol - metabolism ; Diphtheria Toxin - pharmacology ; DNA Fragmentation ; DNA, Complementary - metabolism ; Echocardiography ; Epidermal Growth Factor - metabolism ; Humans ; Immunoblotting ; Immunohistochemistry ; In Situ Hybridization ; In Situ Nick-End Labeling ; Lipopolysaccharides - metabolism ; Lysosomes - metabolism ; Mice ; Mice, Transgenic ; Microscopy, Electron ; Models, Genetic ; Myocardium - pathology ; Myocytes, Cardiac - cytology ; Time Factors ; Transgenes ; Up-Regulation</subject><ispartof>The Journal of biological chemistry, 2004-09, Vol.279 (39), p.41095-41103</ispartof><rights>2004 © 2004 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>Copyright 2004 American Society for Biochemistry and Molecular Biology, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c506t-d0dcf5dc102103c2c1bc75bd1d3851817717205c4bbd1f7df94f237e54095df13</citedby><cites>FETCH-LOGICAL-c506t-d0dcf5dc102103c2c1bc75bd1d3851817717205c4bbd1f7df94f237e54095df13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27911,27912</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15272002$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Akazawa, Hiroshi</creatorcontrib><creatorcontrib>Komazaki, Shinji</creatorcontrib><creatorcontrib>Shimomura, Hiroaki</creatorcontrib><creatorcontrib>Terasaki, Fumio</creatorcontrib><creatorcontrib>Zou, Yunzeng</creatorcontrib><creatorcontrib>Takano, Hiroyuki</creatorcontrib><creatorcontrib>Nagai, Toshio</creatorcontrib><creatorcontrib>Komuro, Issei</creatorcontrib><title>Diphtheria Toxin-induced Autophagic Cardiomyocyte Death Plays a Pathogenic Role in Mouse Model of Heart Failure</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>It is still not clear whether loss of cardiomyocytes through programmed cell death causes heart failure. To clarify the role of cell death in heart failure, we generated transgenic mice (TG) that express human diphtheria toxin receptor in the hearts. A mosaic expression pattern of the transgene was observed, and the transgene-expressing cardiomyocytes (17.3% of the total cardiomyocytes) were diffusely scattered throughout the ventricles. Intramuscular injection of diphtheria toxin induced complete elimination of the transgene-expressing cardiomyocytes within 7 days, and ∼80% of TG showed pathophysiological features characteristic of heart failure and were dead within 14 days. Degenerated cardiomyocytes of the TG heart showed characteristic features indicative of autophagic cell death such as up-regulated lysosomal markers and abundant autophagosomes containing cytosolic organelles like cardiomyocytes of human dilated cardiomyopathy. The heart failure-inducible TG are a useful model for dilated cardiomyopathy, and provided evidence indicating that myocardial cell loss through autophagic cell death plays of a causal role in the pathogenesis heart failure.</description><subject>Animals</subject><subject>Autophagy</subject><subject>Blotting, Northern</subject><subject>Blotting, Western</subject><subject>Cell Death</subject><subject>Cytosol - metabolism</subject><subject>Diphtheria Toxin - pharmacology</subject><subject>DNA Fragmentation</subject><subject>DNA, Complementary - metabolism</subject><subject>Echocardiography</subject><subject>Epidermal Growth Factor - metabolism</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization</subject><subject>In Situ Nick-End Labeling</subject><subject>Lipopolysaccharides - metabolism</subject><subject>Lysosomes - metabolism</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Electron</subject><subject>Models, Genetic</subject><subject>Myocardium - pathology</subject><subject>Myocytes, Cardiac - cytology</subject><subject>Time Factors</subject><subject>Transgenes</subject><subject>Up-Regulation</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEFv1DAQRi1ERZfClSPyAXHL1mPHJDlW25YitWpVFYmb5diTjaskXuwE2H_PoF2pJ3ywNdab0TePsQ8g1iCq8vy5des7BUrUpRTiFVuBqFWhNPx4zVZCSCgaqetT9jbnZ0GnbOANOwUtK8LlisXLsOvnHlOw_Cn-CVMRJr849PximeOut9vg-MYmH-K4j24_I79EO_f8YbD7zC1_oCJucSLsMQ7Iw8Tv4pKRbo8Djx2_QZtmfm3DsCR8x046O2R8f3zP2Pfrq6fNTXF7__Xb5uK2cFp8mQsvvOu0d0AbCOWkg9ZVuvXgVa2hhqoCWkC7sqW_rvJdU3ZSVahL0WjfgTpjnw9zdyn-XDDPZgzZ4TDYCSmekaDqsoaSwPUBdCnmnLAzuxRGm_YGhPmn2JBi86KYGj4eJy_tiP4FPzol4NMB6MO2_x0SmjZE1-NoZNUY1ZgSKCRh9QFD0vArYDLZBZxIPbW42fgY_hfhLwqklfM</recordid><startdate>20040924</startdate><enddate>20040924</enddate><creator>Akazawa, Hiroshi</creator><creator>Komazaki, Shinji</creator><creator>Shimomura, Hiroaki</creator><creator>Terasaki, Fumio</creator><creator>Zou, Yunzeng</creator><creator>Takano, Hiroyuki</creator><creator>Nagai, Toshio</creator><creator>Komuro, Issei</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</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>7U7</scope><scope>C1K</scope></search><sort><creationdate>20040924</creationdate><title>Diphtheria Toxin-induced Autophagic Cardiomyocyte Death Plays a Pathogenic Role in Mouse Model of Heart Failure</title><author>Akazawa, Hiroshi ; Komazaki, Shinji ; Shimomura, Hiroaki ; Terasaki, Fumio ; Zou, Yunzeng ; Takano, Hiroyuki ; Nagai, Toshio ; Komuro, Issei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c506t-d0dcf5dc102103c2c1bc75bd1d3851817717205c4bbd1f7df94f237e54095df13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Autophagy</topic><topic>Blotting, Northern</topic><topic>Blotting, Western</topic><topic>Cell Death</topic><topic>Cytosol - metabolism</topic><topic>Diphtheria Toxin - pharmacology</topic><topic>DNA Fragmentation</topic><topic>DNA, Complementary - metabolism</topic><topic>Echocardiography</topic><topic>Epidermal Growth Factor - metabolism</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Immunohistochemistry</topic><topic>In Situ Hybridization</topic><topic>In Situ Nick-End Labeling</topic><topic>Lipopolysaccharides - metabolism</topic><topic>Lysosomes - metabolism</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Microscopy, Electron</topic><topic>Models, Genetic</topic><topic>Myocardium - pathology</topic><topic>Myocytes, Cardiac - cytology</topic><topic>Time Factors</topic><topic>Transgenes</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Akazawa, Hiroshi</creatorcontrib><creatorcontrib>Komazaki, Shinji</creatorcontrib><creatorcontrib>Shimomura, Hiroaki</creatorcontrib><creatorcontrib>Terasaki, Fumio</creatorcontrib><creatorcontrib>Zou, Yunzeng</creatorcontrib><creatorcontrib>Takano, Hiroyuki</creatorcontrib><creatorcontrib>Nagai, Toshio</creatorcontrib><creatorcontrib>Komuro, Issei</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Akazawa, Hiroshi</au><au>Komazaki, Shinji</au><au>Shimomura, Hiroaki</au><au>Terasaki, Fumio</au><au>Zou, Yunzeng</au><au>Takano, Hiroyuki</au><au>Nagai, Toshio</au><au>Komuro, Issei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diphtheria Toxin-induced Autophagic Cardiomyocyte Death Plays a Pathogenic Role in Mouse Model of Heart Failure</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2004-09-24</date><risdate>2004</risdate><volume>279</volume><issue>39</issue><spage>41095</spage><epage>41103</epage><pages>41095-41103</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>It is still not clear whether loss of cardiomyocytes through programmed cell death causes heart failure. To clarify the role of cell death in heart failure, we generated transgenic mice (TG) that express human diphtheria toxin receptor in the hearts. A mosaic expression pattern of the transgene was observed, and the transgene-expressing cardiomyocytes (17.3% of the total cardiomyocytes) were diffusely scattered throughout the ventricles. Intramuscular injection of diphtheria toxin induced complete elimination of the transgene-expressing cardiomyocytes within 7 days, and ∼80% of TG showed pathophysiological features characteristic of heart failure and were dead within 14 days. Degenerated cardiomyocytes of the TG heart showed characteristic features indicative of autophagic cell death such as up-regulated lysosomal markers and abundant autophagosomes containing cytosolic organelles like cardiomyocytes of human dilated cardiomyopathy. The heart failure-inducible TG are a useful model for dilated cardiomyopathy, and provided evidence indicating that myocardial cell loss through autophagic cell death plays of a causal role in the pathogenesis heart failure.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15272002</pmid><doi>10.1074/jbc.M313084200</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 2004-09, Vol.279 (39), p.41095-41103 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_21384814 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Autophagy Blotting, Northern Blotting, Western Cell Death Cytosol - metabolism Diphtheria Toxin - pharmacology DNA Fragmentation DNA, Complementary - metabolism Echocardiography Epidermal Growth Factor - metabolism Humans Immunoblotting Immunohistochemistry In Situ Hybridization In Situ Nick-End Labeling Lipopolysaccharides - metabolism Lysosomes - metabolism Mice Mice, Transgenic Microscopy, Electron Models, Genetic Myocardium - pathology Myocytes, Cardiac - cytology Time Factors Transgenes Up-Regulation |
| title | Diphtheria Toxin-induced Autophagic Cardiomyocyte Death Plays a Pathogenic Role in Mouse Model of Heart Failure |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T15%3A45%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Diphtheria%20Toxin-induced%20Autophagic%20Cardiomyocyte%20Death%20Plays%20a%20Pathogenic%20Role%20in%20Mouse%20Model%20of%20Heart%20Failure&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=Akazawa,%20Hiroshi&rft.date=2004-09-24&rft.volume=279&rft.issue=39&rft.spage=41095&rft.epage=41103&rft.pages=41095-41103&rft.issn=0021-9258&rft.eissn=1083-351X&rft_id=info:doi/10.1074/jbc.M313084200&rft_dat=%3Cproquest_cross%3E21384814%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=21384814&rft_id=info:pmid/15272002&rft_els_id=S002192582077208X&rfr_iscdi=true |