Inorganic mercury attenuates CD95-mediated apoptosis by interfering with formation of the death inducing signaling complex
Inorganic mercury (Hg 2+) modulates several lymphocyte signaling pathways and has been implicated as an environmental factor linked to autoimmune disease. From the standpoint that autoimmune diseases represent disorders of cell accumulation, in which dysregulated apoptosis may be one mechanism leadi...
Gespeichert in:
| Veröffentlicht in: | Toxicology and applied pharmacology 2003-07, Vol.190 (2), p.146-156 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 156 |
|---|---|
| container_issue | 2 |
| container_start_page | 146 |
| container_title | Toxicology and applied pharmacology |
| container_volume | 190 |
| creator | McCabe, Michael J Whitekus, Michael J Hyun, Joogyung Eckles, Kevin G McCollum, Geniece Rosenspire, Allen J |
| description | Inorganic mercury (Hg
2+) modulates several lymphocyte signaling pathways and has been implicated as an environmental factor linked to autoimmune disease. From the standpoint that autoimmune diseases represent disorders of cell accumulation, in which dysregulated apoptosis may be one mechanism leading to the accumulation of autoreactive lymphocytes, we have been investigating the influences of Hg
2+ on CD95-mediated apoptosis. We demonstrate here that low and noncytotoxic concentrations of Hg
2+ impair CD95 agonist-induced apoptosis in representative Type-I and Type-II T cell lines. Hg
2+ treatment blocks the CD95 agonist-induced activation of initiator and effector caspases as well as the association between CD95 and the signaling adaptor, FADD. CD95 multimerization does not appear to be affected by Hg
2+. Thus, the Hg
2+ sensitive step within the CD95 death pathway is localized to the level of the death inducing signaling complex (DISC). Disruption of proper DISC formation may be a biochemical mechanism whereby Hg
2+ contributes to autoimmune disease. |
| doi_str_mv | 10.1016/S0041-008X(03)00159-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_73510188</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0041008X03001595</els_id><sourcerecordid>18818986</sourcerecordid><originalsourceid>FETCH-LOGICAL-c422t-6fd291ad4ff6d1d50164b762edae39297702d7f779cf6e4a7aa7aa3fadc855103</originalsourceid><addsrcrecordid>eNqFkUuPFCEUhYnROO3oT9Cw0eii9FIvitXEtK9JJnGhJu4IDZceTBWUQKntr5ea7jjLSUjgku_CPecQ8pTBawasf_MFoGUVwPD9JTSvAFgnqu4e2TAQfQVN09wnm__IGXmU0g8AEG3LHpIzVg98gLbdkL-XPsS98k7TCaNe4oGqnNEvKmOi23eiqyY0rlSGqjnMOSSX6O5Anc8YLUbn9_S3y9fUhjip7IKnwdJ8jdSgKtfOm0WvUHJ7r8b1pMM0j_jnMXlg1ZjwyWk_J98-vP-6_VRdff54uX17Vem2rnPVW1MLpkxrbW-Y6Yr4dsf7Go3CRtSCc6gNt5wLbXtsFVfraqwyeug6Bs05eXF8d47h54Ipy8kljeOoPIYlSd4Uig3DnWBh2CCGvoDdEdQxpBTRyjm6ScWDZCDXdORNOnK1XkIjb9KRXel7dvpg2RVXb7tOcRTg-QlQSavRRuW1S7dcEc9FvUq6OHJYfPvlMMqkHXpdkoqoszTB3THKPwbjrnw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>18818986</pqid></control><display><type>article</type><title>Inorganic mercury attenuates CD95-mediated apoptosis by interfering with formation of the death inducing signaling complex</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>McCabe, Michael J ; Whitekus, Michael J ; Hyun, Joogyung ; Eckles, Kevin G ; McCollum, Geniece ; Rosenspire, Allen J</creator><creatorcontrib>McCabe, Michael J ; Whitekus, Michael J ; Hyun, Joogyung ; Eckles, Kevin G ; McCollum, Geniece ; Rosenspire, Allen J</creatorcontrib><description>Inorganic mercury (Hg
2+) modulates several lymphocyte signaling pathways and has been implicated as an environmental factor linked to autoimmune disease. From the standpoint that autoimmune diseases represent disorders of cell accumulation, in which dysregulated apoptosis may be one mechanism leading to the accumulation of autoreactive lymphocytes, we have been investigating the influences of Hg
2+ on CD95-mediated apoptosis. We demonstrate here that low and noncytotoxic concentrations of Hg
2+ impair CD95 agonist-induced apoptosis in representative Type-I and Type-II T cell lines. Hg
2+ treatment blocks the CD95 agonist-induced activation of initiator and effector caspases as well as the association between CD95 and the signaling adaptor, FADD. CD95 multimerization does not appear to be affected by Hg
2+. Thus, the Hg
2+ sensitive step within the CD95 death pathway is localized to the level of the death inducing signaling complex (DISC). Disruption of proper DISC formation may be a biochemical mechanism whereby Hg
2+ contributes to autoimmune disease.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/S0041-008X(03)00159-5</identifier><identifier>PMID: 12878044</identifier><identifier>CODEN: TXAPA9</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>Apoptosis ; Apoptosis - drug effects ; Apoptosis - immunology ; Autoimmunity ; Biological and medical sciences ; CD95 ; Chemical and industrial products toxicology. Toxic occupational diseases ; DISC ; Dose-Response Relationship, Drug ; fas Receptor - immunology ; Human ; Humans ; Jurkat Cells ; Medical sciences ; Mercury ; Mercury - pharmacology ; Metals and various inorganic compounds ; Signal Transduction - immunology ; T lymphocytes ; T-Lymphocytes - drug effects ; T-Lymphocytes - pathology ; Toxicology</subject><ispartof>Toxicology and applied pharmacology, 2003-07, Vol.190 (2), p.146-156</ispartof><rights>2003 Elsevier Science (USA)</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-6fd291ad4ff6d1d50164b762edae39297702d7f779cf6e4a7aa7aa3fadc855103</citedby><cites>FETCH-LOGICAL-c422t-6fd291ad4ff6d1d50164b762edae39297702d7f779cf6e4a7aa7aa3fadc855103</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0041-008X(03)00159-5$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3554,27933,27934,46004</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15017920$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12878044$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McCabe, Michael J</creatorcontrib><creatorcontrib>Whitekus, Michael J</creatorcontrib><creatorcontrib>Hyun, Joogyung</creatorcontrib><creatorcontrib>Eckles, Kevin G</creatorcontrib><creatorcontrib>McCollum, Geniece</creatorcontrib><creatorcontrib>Rosenspire, Allen J</creatorcontrib><title>Inorganic mercury attenuates CD95-mediated apoptosis by interfering with formation of the death inducing signaling complex</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>Inorganic mercury (Hg
2+) modulates several lymphocyte signaling pathways and has been implicated as an environmental factor linked to autoimmune disease. From the standpoint that autoimmune diseases represent disorders of cell accumulation, in which dysregulated apoptosis may be one mechanism leading to the accumulation of autoreactive lymphocytes, we have been investigating the influences of Hg
2+ on CD95-mediated apoptosis. We demonstrate here that low and noncytotoxic concentrations of Hg
2+ impair CD95 agonist-induced apoptosis in representative Type-I and Type-II T cell lines. Hg
2+ treatment blocks the CD95 agonist-induced activation of initiator and effector caspases as well as the association between CD95 and the signaling adaptor, FADD. CD95 multimerization does not appear to be affected by Hg
2+. Thus, the Hg
2+ sensitive step within the CD95 death pathway is localized to the level of the death inducing signaling complex (DISC). Disruption of proper DISC formation may be a biochemical mechanism whereby Hg
2+ contributes to autoimmune disease.</description><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - immunology</subject><subject>Autoimmunity</subject><subject>Biological and medical sciences</subject><subject>CD95</subject><subject>Chemical and industrial products toxicology. Toxic occupational diseases</subject><subject>DISC</subject><subject>Dose-Response Relationship, Drug</subject><subject>fas Receptor - immunology</subject><subject>Human</subject><subject>Humans</subject><subject>Jurkat Cells</subject><subject>Medical sciences</subject><subject>Mercury</subject><subject>Mercury - pharmacology</subject><subject>Metals and various inorganic compounds</subject><subject>Signal Transduction - immunology</subject><subject>T lymphocytes</subject><subject>T-Lymphocytes - drug effects</subject><subject>T-Lymphocytes - pathology</subject><subject>Toxicology</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUuPFCEUhYnROO3oT9Cw0eii9FIvitXEtK9JJnGhJu4IDZceTBWUQKntr5ea7jjLSUjgku_CPecQ8pTBawasf_MFoGUVwPD9JTSvAFgnqu4e2TAQfQVN09wnm__IGXmU0g8AEG3LHpIzVg98gLbdkL-XPsS98k7TCaNe4oGqnNEvKmOi23eiqyY0rlSGqjnMOSSX6O5Anc8YLUbn9_S3y9fUhjip7IKnwdJ8jdSgKtfOm0WvUHJ7r8b1pMM0j_jnMXlg1ZjwyWk_J98-vP-6_VRdff54uX17Vem2rnPVW1MLpkxrbW-Y6Yr4dsf7Go3CRtSCc6gNt5wLbXtsFVfraqwyeug6Bs05eXF8d47h54Ipy8kljeOoPIYlSd4Uig3DnWBh2CCGvoDdEdQxpBTRyjm6ScWDZCDXdORNOnK1XkIjb9KRXel7dvpg2RVXb7tOcRTg-QlQSavRRuW1S7dcEc9FvUq6OHJYfPvlMMqkHXpdkoqoszTB3THKPwbjrnw</recordid><startdate>20030715</startdate><enddate>20030715</enddate><creator>McCabe, Michael J</creator><creator>Whitekus, Michael J</creator><creator>Hyun, Joogyung</creator><creator>Eckles, Kevin G</creator><creator>McCollum, Geniece</creator><creator>Rosenspire, Allen J</creator><general>Elsevier Inc</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>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>20030715</creationdate><title>Inorganic mercury attenuates CD95-mediated apoptosis by interfering with formation of the death inducing signaling complex</title><author>McCabe, Michael J ; Whitekus, Michael J ; Hyun, Joogyung ; Eckles, Kevin G ; McCollum, Geniece ; Rosenspire, Allen J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-6fd291ad4ff6d1d50164b762edae39297702d7f779cf6e4a7aa7aa3fadc855103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - immunology</topic><topic>Autoimmunity</topic><topic>Biological and medical sciences</topic><topic>CD95</topic><topic>Chemical and industrial products toxicology. Toxic occupational diseases</topic><topic>DISC</topic><topic>Dose-Response Relationship, Drug</topic><topic>fas Receptor - immunology</topic><topic>Human</topic><topic>Humans</topic><topic>Jurkat Cells</topic><topic>Medical sciences</topic><topic>Mercury</topic><topic>Mercury - pharmacology</topic><topic>Metals and various inorganic compounds</topic><topic>Signal Transduction - immunology</topic><topic>T lymphocytes</topic><topic>T-Lymphocytes - drug effects</topic><topic>T-Lymphocytes - pathology</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McCabe, Michael J</creatorcontrib><creatorcontrib>Whitekus, Michael J</creatorcontrib><creatorcontrib>Hyun, Joogyung</creatorcontrib><creatorcontrib>Eckles, Kevin G</creatorcontrib><creatorcontrib>McCollum, Geniece</creatorcontrib><creatorcontrib>Rosenspire, Allen J</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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McCabe, Michael J</au><au>Whitekus, Michael J</au><au>Hyun, Joogyung</au><au>Eckles, Kevin G</au><au>McCollum, Geniece</au><au>Rosenspire, Allen J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inorganic mercury attenuates CD95-mediated apoptosis by interfering with formation of the death inducing signaling complex</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2003-07-15</date><risdate>2003</risdate><volume>190</volume><issue>2</issue><spage>146</spage><epage>156</epage><pages>146-156</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><coden>TXAPA9</coden><abstract>Inorganic mercury (Hg
2+) modulates several lymphocyte signaling pathways and has been implicated as an environmental factor linked to autoimmune disease. From the standpoint that autoimmune diseases represent disorders of cell accumulation, in which dysregulated apoptosis may be one mechanism leading to the accumulation of autoreactive lymphocytes, we have been investigating the influences of Hg
2+ on CD95-mediated apoptosis. We demonstrate here that low and noncytotoxic concentrations of Hg
2+ impair CD95 agonist-induced apoptosis in representative Type-I and Type-II T cell lines. Hg
2+ treatment blocks the CD95 agonist-induced activation of initiator and effector caspases as well as the association between CD95 and the signaling adaptor, FADD. CD95 multimerization does not appear to be affected by Hg
2+. Thus, the Hg
2+ sensitive step within the CD95 death pathway is localized to the level of the death inducing signaling complex (DISC). Disruption of proper DISC formation may be a biochemical mechanism whereby Hg
2+ contributes to autoimmune disease.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>12878044</pmid><doi>10.1016/S0041-008X(03)00159-5</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0041-008X |
| ispartof | Toxicology and applied pharmacology, 2003-07, Vol.190 (2), p.146-156 |
| issn | 0041-008X 1096-0333 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_73510188 |
| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Apoptosis Apoptosis - drug effects Apoptosis - immunology Autoimmunity Biological and medical sciences CD95 Chemical and industrial products toxicology. Toxic occupational diseases DISC Dose-Response Relationship, Drug fas Receptor - immunology Human Humans Jurkat Cells Medical sciences Mercury Mercury - pharmacology Metals and various inorganic compounds Signal Transduction - immunology T lymphocytes T-Lymphocytes - drug effects T-Lymphocytes - pathology Toxicology |
| title | Inorganic mercury attenuates CD95-mediated apoptosis by interfering with formation of the death inducing signaling complex |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-03T13%3A42%3A45IST&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=Inorganic%20mercury%20attenuates%20CD95-mediated%20apoptosis%20by%20interfering%20with%20formation%20of%20the%20death%20inducing%20signaling%20complex&rft.jtitle=Toxicology%20and%20applied%20pharmacology&rft.au=McCabe,%20Michael%20J&rft.date=2003-07-15&rft.volume=190&rft.issue=2&rft.spage=146&rft.epage=156&rft.pages=146-156&rft.issn=0041-008X&rft.eissn=1096-0333&rft.coden=TXAPA9&rft_id=info:doi/10.1016/S0041-008X(03)00159-5&rft_dat=%3Cproquest_cross%3E18818986%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=18818986&rft_id=info:pmid/12878044&rft_els_id=S0041008X03001595&rfr_iscdi=true |