Anti-recoverin antibodies induce an increase in intracellular calcium, leading to apoptosis in retinal cells
Autoantibodies against recoverin, a Ca 2+-binding protein found in patients with cancer-associated retinopathy (CAR syndrome), penetrate retinal cells and induce their apoptosis via a mitochondrial pathway. The goal of this study was to investigate whether the entry of anti-recoverin antibody into E...
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Veröffentlicht in: | Journal of autoimmunity 2006-03, Vol.26 (2), p.146-153 |
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creator | Adamus, Grazyna Webb, Sarah Shiraga, Sharon Duvoisin, Robert M. |
description | Autoantibodies against recoverin, a Ca
2+-binding protein found in patients with cancer-associated retinopathy (CAR syndrome), penetrate retinal cells and induce their apoptosis via a mitochondrial pathway. The goal of this study was to investigate whether the entry of anti-recoverin antibody into E1A.NR3 retinal cells causes a change in intracellular Ca
2+. Intracellular Ca
2+ was measured using the Ca
2+-sensitive fluorescent dye Fura-2 AM in living E1A.NR3 retinal cells treated with anti-recoverin antibody Rec-1, patients' autoantibodies, and control rat and human IgG. The exposure of retinal cells to Rec-1 antibody and to the CAR patients' autoantibodies in vitro caused a significant increase in intracellular Ca
2+, while non-specific antibodies did not induce such an effect. Co-treatment of the E1A.NR3 cells with Rec-1 in the presence of nifedipine, a L-type Ca
2+ channel blocker, significantly suppressed the increase of Ca
2+. Treatment with nifedipine also blocked changes in the anti-apoptotic protein bcl-xL and in expressions of the pro-apoptotic protein bax. Nifedipine-treated cells also showed a decrease in cytosolic cytochrome
c release and a decrease in caspase 3 activation, compared to cells treated only with Rec-1 antibody. The increase in the antibody-induced Ca
2+ is at least in part dependent on extracellular Ca
2+. Nifedipine was found to inhibit the entry of Ca
2+ into the cells and to protect them from Rec-1-induced apoptosis. Increased levels of intracellular Ca
2+ may lead to retinal dysfunction and degeneration in the CAR syndrome. Our results provide a molecular basis for the use of Ca
2+ blockers in the treatment of the CAR syndrome. |
doi_str_mv | 10.1016/j.jaut.2005.11.007 |
format | Article |
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2+-binding protein found in patients with cancer-associated retinopathy (CAR syndrome), penetrate retinal cells and induce their apoptosis via a mitochondrial pathway. The goal of this study was to investigate whether the entry of anti-recoverin antibody into E1A.NR3 retinal cells causes a change in intracellular Ca
2+. Intracellular Ca
2+ was measured using the Ca
2+-sensitive fluorescent dye Fura-2 AM in living E1A.NR3 retinal cells treated with anti-recoverin antibody Rec-1, patients' autoantibodies, and control rat and human IgG. The exposure of retinal cells to Rec-1 antibody and to the CAR patients' autoantibodies in vitro caused a significant increase in intracellular Ca
2+, while non-specific antibodies did not induce such an effect. Co-treatment of the E1A.NR3 cells with Rec-1 in the presence of nifedipine, a L-type Ca
2+ channel blocker, significantly suppressed the increase of Ca
2+. Treatment with nifedipine also blocked changes in the anti-apoptotic protein bcl-xL and in expressions of the pro-apoptotic protein bax. Nifedipine-treated cells also showed a decrease in cytosolic cytochrome
c release and a decrease in caspase 3 activation, compared to cells treated only with Rec-1 antibody. The increase in the antibody-induced Ca
2+ is at least in part dependent on extracellular Ca
2+. Nifedipine was found to inhibit the entry of Ca
2+ into the cells and to protect them from Rec-1-induced apoptosis. Increased levels of intracellular Ca
2+ may lead to retinal dysfunction and degeneration in the CAR syndrome. Our results provide a molecular basis for the use of Ca
2+ blockers in the treatment of the CAR syndrome.</description><identifier>ISSN: 0896-8411</identifier><identifier>EISSN: 1095-9157</identifier><identifier>DOI: 10.1016/j.jaut.2005.11.007</identifier><identifier>PMID: 16426815</identifier><language>eng</language><publisher>London: Elsevier Ltd</publisher><subject>Animals ; Antibodies, Monoclonal - pharmacology ; Apoptosis - drug effects ; Autoantibodies ; Autoantibodies - pharmacology ; Autoimmunity ; bcl-2-Associated X Protein - metabolism ; bcl-X Protein - metabolism ; Biological and medical sciences ; Calcium ; Calcium - metabolism ; Calcium Channel Blockers - pharmacology ; Calcium Channel Blockers - therapeutic use ; Calcium-Binding Proteins - antagonists & inhibitors ; Calcium-Binding Proteins - immunology ; CAR syndrome ; Cell Line ; Cytochromes c - metabolism ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; General aspects ; Humans ; Immunopathology ; Medical sciences ; Neoplasms - complications ; Neoplasms - immunology ; Nifedipine - pharmacology ; Nifedipine - therapeutic use ; Paraneoplastic syndrome ; Rats ; Recoverin - antagonists & inhibitors ; Recoverin - immunology ; Retina ; Retina - cytology ; Retina - drug effects ; Retina - metabolism ; Retinal Diseases - drug therapy ; Retinal Diseases - immunology ; Retinopathy ; Syndrome</subject><ispartof>Journal of autoimmunity, 2006-03, Vol.26 (2), p.146-153</ispartof><rights>2005 Elsevier Ltd</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-5dadcf5418f0cc41597fcf271a16903058a615df2b92043fb7b85f9c607dbc0e3</citedby><cites>FETCH-LOGICAL-c481t-5dadcf5418f0cc41597fcf271a16903058a615df2b92043fb7b85f9c607dbc0e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jaut.2005.11.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27926,27927,45997</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17604420$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16426815$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Adamus, Grazyna</creatorcontrib><creatorcontrib>Webb, Sarah</creatorcontrib><creatorcontrib>Shiraga, Sharon</creatorcontrib><creatorcontrib>Duvoisin, Robert M.</creatorcontrib><title>Anti-recoverin antibodies induce an increase in intracellular calcium, leading to apoptosis in retinal cells</title><title>Journal of autoimmunity</title><addtitle>J Autoimmun</addtitle><description>Autoantibodies against recoverin, a Ca
2+-binding protein found in patients with cancer-associated retinopathy (CAR syndrome), penetrate retinal cells and induce their apoptosis via a mitochondrial pathway. The goal of this study was to investigate whether the entry of anti-recoverin antibody into E1A.NR3 retinal cells causes a change in intracellular Ca
2+. Intracellular Ca
2+ was measured using the Ca
2+-sensitive fluorescent dye Fura-2 AM in living E1A.NR3 retinal cells treated with anti-recoverin antibody Rec-1, patients' autoantibodies, and control rat and human IgG. The exposure of retinal cells to Rec-1 antibody and to the CAR patients' autoantibodies in vitro caused a significant increase in intracellular Ca
2+, while non-specific antibodies did not induce such an effect. Co-treatment of the E1A.NR3 cells with Rec-1 in the presence of nifedipine, a L-type Ca
2+ channel blocker, significantly suppressed the increase of Ca
2+. Treatment with nifedipine also blocked changes in the anti-apoptotic protein bcl-xL and in expressions of the pro-apoptotic protein bax. Nifedipine-treated cells also showed a decrease in cytosolic cytochrome
c release and a decrease in caspase 3 activation, compared to cells treated only with Rec-1 antibody. The increase in the antibody-induced Ca
2+ is at least in part dependent on extracellular Ca
2+. Nifedipine was found to inhibit the entry of Ca
2+ into the cells and to protect them from Rec-1-induced apoptosis. Increased levels of intracellular Ca
2+ may lead to retinal dysfunction and degeneration in the CAR syndrome. Our results provide a molecular basis for the use of Ca
2+ blockers in the treatment of the CAR syndrome.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Autoantibodies</subject><subject>Autoantibodies - pharmacology</subject><subject>Autoimmunity</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>bcl-X Protein - metabolism</subject><subject>Biological and medical sciences</subject><subject>Calcium</subject><subject>Calcium - metabolism</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Calcium Channel Blockers - therapeutic use</subject><subject>Calcium-Binding Proteins - antagonists & inhibitors</subject><subject>Calcium-Binding Proteins - immunology</subject><subject>CAR syndrome</subject><subject>Cell Line</subject><subject>Cytochromes c - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>General aspects</subject><subject>Humans</subject><subject>Immunopathology</subject><subject>Medical sciences</subject><subject>Neoplasms - complications</subject><subject>Neoplasms - immunology</subject><subject>Nifedipine - pharmacology</subject><subject>Nifedipine - therapeutic use</subject><subject>Paraneoplastic syndrome</subject><subject>Rats</subject><subject>Recoverin - antagonists & inhibitors</subject><subject>Recoverin - immunology</subject><subject>Retina</subject><subject>Retina - cytology</subject><subject>Retina - drug effects</subject><subject>Retina - metabolism</subject><subject>Retinal Diseases - drug therapy</subject><subject>Retinal Diseases - immunology</subject><subject>Retinopathy</subject><subject>Syndrome</subject><issn>0896-8411</issn><issn>1095-9157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFr3DAQhUVpSTZp_kAPxZf2FLsztiTL0EsISVsI9NKehSyNihavvZXkQP99ZXYhtxYEGonvPYb3GHuH0CCg_LRv9mbNTQsgGsQGoH_FdgiDqAcU_Wu2AzXIWnHES3aV0h4AUQhxwS5R8lYqFDs23c051JHs8kwxzJUpz3FxgVIVZrdaKj9lspFMojKUk6OxNE3rZGJlzWTDeritJjIuzL-qvFTmuBzzksLmUEXKYTZTtSnSW_bGmynRzfm-Zj8fH37cf62fvn_5dn_3VFuuMNfCGWe94Kg8WMtRDL23vu3RoBygA6GMROF8Ow4t8M6P_aiEH6yE3o0WqLtmH0--x7j8XillfQhp28DMtKxJ9yBVB1z9F8QeoQXVFbA9gTYuKUXy-hjDwcQ_GkFvZei93srQWxkaUZcyiuj92X0dD-ReJOf0C_DhDJhUkvTRzDakF66XwHkLhft84qiE9hwo6mQDzZZcKM1l7Zbwrz3-AoaZqUE</recordid><startdate>20060301</startdate><enddate>20060301</enddate><creator>Adamus, Grazyna</creator><creator>Webb, Sarah</creator><creator>Shiraga, Sharon</creator><creator>Duvoisin, Robert M.</creator><general>Elsevier Ltd</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20060301</creationdate><title>Anti-recoverin antibodies induce an increase in intracellular calcium, leading to apoptosis in retinal cells</title><author>Adamus, Grazyna ; Webb, Sarah ; Shiraga, Sharon ; Duvoisin, Robert M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-5dadcf5418f0cc41597fcf271a16903058a615df2b92043fb7b85f9c607dbc0e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Autoantibodies</topic><topic>Autoantibodies - pharmacology</topic><topic>Autoimmunity</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>bcl-X Protein - metabolism</topic><topic>Biological and medical sciences</topic><topic>Calcium</topic><topic>Calcium - metabolism</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Calcium Channel Blockers - therapeutic use</topic><topic>Calcium-Binding Proteins - antagonists & inhibitors</topic><topic>Calcium-Binding Proteins - immunology</topic><topic>CAR syndrome</topic><topic>Cell Line</topic><topic>Cytochromes c - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>General aspects</topic><topic>Humans</topic><topic>Immunopathology</topic><topic>Medical sciences</topic><topic>Neoplasms - complications</topic><topic>Neoplasms - immunology</topic><topic>Nifedipine - pharmacology</topic><topic>Nifedipine - therapeutic use</topic><topic>Paraneoplastic syndrome</topic><topic>Rats</topic><topic>Recoverin - antagonists & inhibitors</topic><topic>Recoverin - immunology</topic><topic>Retina</topic><topic>Retina - cytology</topic><topic>Retina - drug effects</topic><topic>Retina - metabolism</topic><topic>Retinal Diseases - drug therapy</topic><topic>Retinal Diseases - immunology</topic><topic>Retinopathy</topic><topic>Syndrome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Adamus, Grazyna</creatorcontrib><creatorcontrib>Webb, Sarah</creatorcontrib><creatorcontrib>Shiraga, Sharon</creatorcontrib><creatorcontrib>Duvoisin, Robert M.</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of autoimmunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Adamus, Grazyna</au><au>Webb, Sarah</au><au>Shiraga, Sharon</au><au>Duvoisin, Robert M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-recoverin antibodies induce an increase in intracellular calcium, leading to apoptosis in retinal cells</atitle><jtitle>Journal of autoimmunity</jtitle><addtitle>J Autoimmun</addtitle><date>2006-03-01</date><risdate>2006</risdate><volume>26</volume><issue>2</issue><spage>146</spage><epage>153</epage><pages>146-153</pages><issn>0896-8411</issn><eissn>1095-9157</eissn><abstract>Autoantibodies against recoverin, a Ca
2+-binding protein found in patients with cancer-associated retinopathy (CAR syndrome), penetrate retinal cells and induce their apoptosis via a mitochondrial pathway. The goal of this study was to investigate whether the entry of anti-recoverin antibody into E1A.NR3 retinal cells causes a change in intracellular Ca
2+. Intracellular Ca
2+ was measured using the Ca
2+-sensitive fluorescent dye Fura-2 AM in living E1A.NR3 retinal cells treated with anti-recoverin antibody Rec-1, patients' autoantibodies, and control rat and human IgG. The exposure of retinal cells to Rec-1 antibody and to the CAR patients' autoantibodies in vitro caused a significant increase in intracellular Ca
2+, while non-specific antibodies did not induce such an effect. Co-treatment of the E1A.NR3 cells with Rec-1 in the presence of nifedipine, a L-type Ca
2+ channel blocker, significantly suppressed the increase of Ca
2+. Treatment with nifedipine also blocked changes in the anti-apoptotic protein bcl-xL and in expressions of the pro-apoptotic protein bax. Nifedipine-treated cells also showed a decrease in cytosolic cytochrome
c release and a decrease in caspase 3 activation, compared to cells treated only with Rec-1 antibody. The increase in the antibody-induced Ca
2+ is at least in part dependent on extracellular Ca
2+. Nifedipine was found to inhibit the entry of Ca
2+ into the cells and to protect them from Rec-1-induced apoptosis. Increased levels of intracellular Ca
2+ may lead to retinal dysfunction and degeneration in the CAR syndrome. Our results provide a molecular basis for the use of Ca
2+ blockers in the treatment of the CAR syndrome.</abstract><cop>London</cop><pub>Elsevier Ltd</pub><pmid>16426815</pmid><doi>10.1016/j.jaut.2005.11.007</doi><tpages>8</tpages></addata></record> |
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subjects | Animals Antibodies, Monoclonal - pharmacology Apoptosis - drug effects Autoantibodies Autoantibodies - pharmacology Autoimmunity bcl-2-Associated X Protein - metabolism bcl-X Protein - metabolism Biological and medical sciences Calcium Calcium - metabolism Calcium Channel Blockers - pharmacology Calcium Channel Blockers - therapeutic use Calcium-Binding Proteins - antagonists & inhibitors Calcium-Binding Proteins - immunology CAR syndrome Cell Line Cytochromes c - metabolism Fundamental and applied biological sciences. Psychology Fundamental immunology General aspects Humans Immunopathology Medical sciences Neoplasms - complications Neoplasms - immunology Nifedipine - pharmacology Nifedipine - therapeutic use Paraneoplastic syndrome Rats Recoverin - antagonists & inhibitors Recoverin - immunology Retina Retina - cytology Retina - drug effects Retina - metabolism Retinal Diseases - drug therapy Retinal Diseases - immunology Retinopathy Syndrome |
title | Anti-recoverin antibodies induce an increase in intracellular calcium, leading to apoptosis in retinal cells |
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