Calpains mediate epithelial-cell death during mammary gland involution: mitochondria and lysosomal destabilization
Our aim was to elucidate the physiological role of calpains (CAPN) in mammary gland involution. Both CAPN-1 and -2 were induced after weaning and its activity increased in isolated mitochondria and lysosomes. CAPN activation within the mitochondria could trigger the release of cytochrome c and other...
Gespeichert in:
| Veröffentlicht in: | Cell death and differentiation 2012-09, Vol.19 (9), p.1536-1548 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1548 |
|---|---|
| container_issue | 9 |
| container_start_page | 1536 |
| container_title | Cell death and differentiation |
| container_volume | 19 |
| creator | Arnandis, T Ferrer-Vicens, I García-Trevijano, E R Miralles, V J García, C Torres, L Viña, J R Zaragozá, R |
| description | Our aim was to elucidate the physiological role of calpains (CAPN) in mammary gland involution. Both CAPN-1 and -2 were induced after weaning and its activity increased in isolated mitochondria and lysosomes. CAPN activation within the mitochondria could trigger the release of cytochrome
c
and other pro-apoptotic factors, whereas in lysosomes it might be essential for tissue remodeling by releasing cathepsins into the cytosol. Immunohistochemical analysis localized CAPNs mainly at the luminal side of alveoli. During weaning, CAPNs translocate to the lysosomes processing membrane proteins. To identify these substrates, lysosomal fractions were treated with recombinant CAPN and cleaved products were identified by 2D-DIGE. The subunit b
2
of the v-type H
+
ATPase is proteolyzed and so is the lysosomal-associated membrane protein 2a (LAMP2a). Both proteins are also cleaved
in vivo
. Furthermore, LAMP2a cleavage was confirmed
in vitro
by addition of CAPNs to isolated lysosomes and several CAPN inhibitors prevented it. Finally,
in vivo
inhibition of CAPN1 in 72-h-weaned mice decreased LAMP2a cleavage. Indeed, calpeptin-treated mice showed a substantial delay in tissue remodeling and involution of the mammary gland. These results suggest that CAPNs are responsible for mitochondrial and lysosomal membrane permeabilization, supporting the idea that lysosomal-mediated cell death is a new hallmark of mammary gland involution. |
| doi_str_mv | 10.1038/cdd.2012.46 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3422479</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1033535014</sourcerecordid><originalsourceid>FETCH-LOGICAL-c512t-2f422783084bba80d49c0b90232abfbbb5aea0d596ce45bca5d7a569294c96ad3</originalsourceid><addsrcrecordid>eNplkUuLFDEUhYMozkNX7qXAjTBWm3dVzUKQxhcMuNF1uHl0d4ZUUiZVA-OvN2WPw6irBO7Hufecg9ALgjcEs_6tsXZDMaEbLh-hU8I72QqO2eP6ZwK3A-bdCTor5RpjLLtBPkUnlAohuGCnKG8hTOBjaUZnPcyucZOfDy54CK1xITTWwXxo7JJ93DcjjCPk22YfINrGx5sUltmneNmMfk7mkKLNHpp1GG5LKmmEVaHMoH3wP2Fln6EnOwjFPb97z9H3jx--bT-3V18_fdm-v2qNIHRu6Y5T2vUM91xr6LHlg8F6wJRR0DuttQAH2IpBGseFNiBsB0IOdOBmkGDZOXp31J0WXc0ZF-cMQU3ZrxZUAq_-nkR_UPt0o1hdzLuhCry-E8jpx1JNqNGXNROILi1F1fSZqBETXtFX_6DXacmx2vtNEdkRwip1caRMTqVkt7s_huCV61XtUq1dKi4r_fLh_ffsn_Iq8OYIlGktx-WHS__X-wU7kKwh</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1033167113</pqid></control><display><type>article</type><title>Calpains mediate epithelial-cell death during mammary gland involution: mitochondria and lysosomal destabilization</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>SpringerLink Journals - AutoHoldings</source><creator>Arnandis, T ; Ferrer-Vicens, I ; García-Trevijano, E R ; Miralles, V J ; García, C ; Torres, L ; Viña, J R ; Zaragozá, R</creator><creatorcontrib>Arnandis, T ; Ferrer-Vicens, I ; García-Trevijano, E R ; Miralles, V J ; García, C ; Torres, L ; Viña, J R ; Zaragozá, R</creatorcontrib><description>Our aim was to elucidate the physiological role of calpains (CAPN) in mammary gland involution. Both CAPN-1 and -2 were induced after weaning and its activity increased in isolated mitochondria and lysosomes. CAPN activation within the mitochondria could trigger the release of cytochrome
c
and other pro-apoptotic factors, whereas in lysosomes it might be essential for tissue remodeling by releasing cathepsins into the cytosol. Immunohistochemical analysis localized CAPNs mainly at the luminal side of alveoli. During weaning, CAPNs translocate to the lysosomes processing membrane proteins. To identify these substrates, lysosomal fractions were treated with recombinant CAPN and cleaved products were identified by 2D-DIGE. The subunit b
2
of the v-type H
+
ATPase is proteolyzed and so is the lysosomal-associated membrane protein 2a (LAMP2a). Both proteins are also cleaved
in vivo
. Furthermore, LAMP2a cleavage was confirmed
in vitro
by addition of CAPNs to isolated lysosomes and several CAPN inhibitors prevented it. Finally,
in vivo
inhibition of CAPN1 in 72-h-weaned mice decreased LAMP2a cleavage. Indeed, calpeptin-treated mice showed a substantial delay in tissue remodeling and involution of the mammary gland. These results suggest that CAPNs are responsible for mitochondrial and lysosomal membrane permeabilization, supporting the idea that lysosomal-mediated cell death is a new hallmark of mammary gland involution.</description><identifier>ISSN: 1350-9047</identifier><identifier>EISSN: 1476-5403</identifier><identifier>DOI: 10.1038/cdd.2012.46</identifier><identifier>PMID: 22555453</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/45/607/1164 ; 631/80/642/1624 ; 631/80/642/333 ; 631/80/82/23 ; Animals ; Apoptosis ; Biochemistry ; Biomedical and Life Sciences ; Calpain - metabolism ; Cathepsins - metabolism ; Cell Biology ; Cell Cycle Analysis ; Cell death ; Enzyme Activation ; Epithelial Cells - cytology ; Epithelial Cells - enzymology ; Female ; Life Sciences ; Lysosomal-Associated Membrane Protein 2 - metabolism ; Lysosomes - enzymology ; Mammary Glands, Animal - cytology ; Mammary Glands, Animal - metabolism ; Mice ; Mitochondria - enzymology ; Mitochondrial Proteins - metabolism ; Original Paper ; Proteolysis ; Stem Cells</subject><ispartof>Cell death and differentiation, 2012-09, Vol.19 (9), p.1536-1548</ispartof><rights>Macmillan Publishers Limited 2012</rights><rights>Copyright Nature Publishing Group Sep 2012</rights><rights>Copyright © 2012 Macmillan Publishers Limited 2012 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c512t-2f422783084bba80d49c0b90232abfbbb5aea0d596ce45bca5d7a569294c96ad3</citedby><cites>FETCH-LOGICAL-c512t-2f422783084bba80d49c0b90232abfbbb5aea0d596ce45bca5d7a569294c96ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422479/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422479/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,41488,42557,51319,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22555453$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arnandis, T</creatorcontrib><creatorcontrib>Ferrer-Vicens, I</creatorcontrib><creatorcontrib>García-Trevijano, E R</creatorcontrib><creatorcontrib>Miralles, V J</creatorcontrib><creatorcontrib>García, C</creatorcontrib><creatorcontrib>Torres, L</creatorcontrib><creatorcontrib>Viña, J R</creatorcontrib><creatorcontrib>Zaragozá, R</creatorcontrib><title>Calpains mediate epithelial-cell death during mammary gland involution: mitochondria and lysosomal destabilization</title><title>Cell death and differentiation</title><addtitle>Cell Death Differ</addtitle><addtitle>Cell Death Differ</addtitle><description>Our aim was to elucidate the physiological role of calpains (CAPN) in mammary gland involution. Both CAPN-1 and -2 were induced after weaning and its activity increased in isolated mitochondria and lysosomes. CAPN activation within the mitochondria could trigger the release of cytochrome
c
and other pro-apoptotic factors, whereas in lysosomes it might be essential for tissue remodeling by releasing cathepsins into the cytosol. Immunohistochemical analysis localized CAPNs mainly at the luminal side of alveoli. During weaning, CAPNs translocate to the lysosomes processing membrane proteins. To identify these substrates, lysosomal fractions were treated with recombinant CAPN and cleaved products were identified by 2D-DIGE. The subunit b
2
of the v-type H
+
ATPase is proteolyzed and so is the lysosomal-associated membrane protein 2a (LAMP2a). Both proteins are also cleaved
in vivo
. Furthermore, LAMP2a cleavage was confirmed
in vitro
by addition of CAPNs to isolated lysosomes and several CAPN inhibitors prevented it. Finally,
in vivo
inhibition of CAPN1 in 72-h-weaned mice decreased LAMP2a cleavage. Indeed, calpeptin-treated mice showed a substantial delay in tissue remodeling and involution of the mammary gland. These results suggest that CAPNs are responsible for mitochondrial and lysosomal membrane permeabilization, supporting the idea that lysosomal-mediated cell death is a new hallmark of mammary gland involution.</description><subject>631/45/607/1164</subject><subject>631/80/642/1624</subject><subject>631/80/642/333</subject><subject>631/80/82/23</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Calpain - metabolism</subject><subject>Cathepsins - metabolism</subject><subject>Cell Biology</subject><subject>Cell Cycle Analysis</subject><subject>Cell death</subject><subject>Enzyme Activation</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - enzymology</subject><subject>Female</subject><subject>Life Sciences</subject><subject>Lysosomal-Associated Membrane Protein 2 - metabolism</subject><subject>Lysosomes - enzymology</subject><subject>Mammary Glands, Animal - cytology</subject><subject>Mammary Glands, Animal - metabolism</subject><subject>Mice</subject><subject>Mitochondria - enzymology</subject><subject>Mitochondrial Proteins - metabolism</subject><subject>Original Paper</subject><subject>Proteolysis</subject><subject>Stem Cells</subject><issn>1350-9047</issn><issn>1476-5403</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkUuLFDEUhYMozkNX7qXAjTBWm3dVzUKQxhcMuNF1uHl0d4ZUUiZVA-OvN2WPw6irBO7Hufecg9ALgjcEs_6tsXZDMaEbLh-hU8I72QqO2eP6ZwK3A-bdCTor5RpjLLtBPkUnlAohuGCnKG8hTOBjaUZnPcyucZOfDy54CK1xITTWwXxo7JJ93DcjjCPk22YfINrGx5sUltmneNmMfk7mkKLNHpp1GG5LKmmEVaHMoH3wP2Fln6EnOwjFPb97z9H3jx--bT-3V18_fdm-v2qNIHRu6Y5T2vUM91xr6LHlg8F6wJRR0DuttQAH2IpBGseFNiBsB0IOdOBmkGDZOXp31J0WXc0ZF-cMQU3ZrxZUAq_-nkR_UPt0o1hdzLuhCry-E8jpx1JNqNGXNROILi1F1fSZqBETXtFX_6DXacmx2vtNEdkRwip1caRMTqVkt7s_huCV61XtUq1dKi4r_fLh_ffsn_Iq8OYIlGktx-WHS__X-wU7kKwh</recordid><startdate>20120901</startdate><enddate>20120901</enddate><creator>Arnandis, T</creator><creator>Ferrer-Vicens, I</creator><creator>García-Trevijano, E R</creator><creator>Miralles, V J</creator><creator>García, C</creator><creator>Torres, L</creator><creator>Viña, J R</creator><creator>Zaragozá, R</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><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>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120901</creationdate><title>Calpains mediate epithelial-cell death during mammary gland involution: mitochondria and lysosomal destabilization</title><author>Arnandis, T ; Ferrer-Vicens, I ; García-Trevijano, E R ; Miralles, V J ; García, C ; Torres, L ; Viña, J R ; Zaragozá, R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c512t-2f422783084bba80d49c0b90232abfbbb5aea0d596ce45bca5d7a569294c96ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>631/45/607/1164</topic><topic>631/80/642/1624</topic><topic>631/80/642/333</topic><topic>631/80/82/23</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Calpain - metabolism</topic><topic>Cathepsins - metabolism</topic><topic>Cell Biology</topic><topic>Cell Cycle Analysis</topic><topic>Cell death</topic><topic>Enzyme Activation</topic><topic>Epithelial Cells - cytology</topic><topic>Epithelial Cells - enzymology</topic><topic>Female</topic><topic>Life Sciences</topic><topic>Lysosomal-Associated Membrane Protein 2 - metabolism</topic><topic>Lysosomes - enzymology</topic><topic>Mammary Glands, Animal - cytology</topic><topic>Mammary Glands, Animal - metabolism</topic><topic>Mice</topic><topic>Mitochondria - enzymology</topic><topic>Mitochondrial Proteins - metabolism</topic><topic>Original Paper</topic><topic>Proteolysis</topic><topic>Stem Cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arnandis, T</creatorcontrib><creatorcontrib>Ferrer-Vicens, I</creatorcontrib><creatorcontrib>García-Trevijano, E R</creatorcontrib><creatorcontrib>Miralles, V J</creatorcontrib><creatorcontrib>García, C</creatorcontrib><creatorcontrib>Torres, L</creatorcontrib><creatorcontrib>Viña, J R</creatorcontrib><creatorcontrib>Zaragozá, R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death and differentiation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arnandis, T</au><au>Ferrer-Vicens, I</au><au>García-Trevijano, E R</au><au>Miralles, V J</au><au>García, C</au><au>Torres, L</au><au>Viña, J R</au><au>Zaragozá, R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Calpains mediate epithelial-cell death during mammary gland involution: mitochondria and lysosomal destabilization</atitle><jtitle>Cell death and differentiation</jtitle><stitle>Cell Death Differ</stitle><addtitle>Cell Death Differ</addtitle><date>2012-09-01</date><risdate>2012</risdate><volume>19</volume><issue>9</issue><spage>1536</spage><epage>1548</epage><pages>1536-1548</pages><issn>1350-9047</issn><eissn>1476-5403</eissn><abstract>Our aim was to elucidate the physiological role of calpains (CAPN) in mammary gland involution. Both CAPN-1 and -2 were induced after weaning and its activity increased in isolated mitochondria and lysosomes. CAPN activation within the mitochondria could trigger the release of cytochrome
c
and other pro-apoptotic factors, whereas in lysosomes it might be essential for tissue remodeling by releasing cathepsins into the cytosol. Immunohistochemical analysis localized CAPNs mainly at the luminal side of alveoli. During weaning, CAPNs translocate to the lysosomes processing membrane proteins. To identify these substrates, lysosomal fractions were treated with recombinant CAPN and cleaved products were identified by 2D-DIGE. The subunit b
2
of the v-type H
+
ATPase is proteolyzed and so is the lysosomal-associated membrane protein 2a (LAMP2a). Both proteins are also cleaved
in vivo
. Furthermore, LAMP2a cleavage was confirmed
in vitro
by addition of CAPNs to isolated lysosomes and several CAPN inhibitors prevented it. Finally,
in vivo
inhibition of CAPN1 in 72-h-weaned mice decreased LAMP2a cleavage. Indeed, calpeptin-treated mice showed a substantial delay in tissue remodeling and involution of the mammary gland. These results suggest that CAPNs are responsible for mitochondrial and lysosomal membrane permeabilization, supporting the idea that lysosomal-mediated cell death is a new hallmark of mammary gland involution.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>22555453</pmid><doi>10.1038/cdd.2012.46</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1350-9047 |
| ispartof | Cell death and differentiation, 2012-09, Vol.19 (9), p.1536-1548 |
| issn | 1350-9047 1476-5403 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3422479 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; SpringerLink Journals - AutoHoldings |
| subjects | 631/45/607/1164 631/80/642/1624 631/80/642/333 631/80/82/23 Animals Apoptosis Biochemistry Biomedical and Life Sciences Calpain - metabolism Cathepsins - metabolism Cell Biology Cell Cycle Analysis Cell death Enzyme Activation Epithelial Cells - cytology Epithelial Cells - enzymology Female Life Sciences Lysosomal-Associated Membrane Protein 2 - metabolism Lysosomes - enzymology Mammary Glands, Animal - cytology Mammary Glands, Animal - metabolism Mice Mitochondria - enzymology Mitochondrial Proteins - metabolism Original Paper Proteolysis Stem Cells |
| title | Calpains mediate epithelial-cell death during mammary gland involution: mitochondria and lysosomal destabilization |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T23%3A31%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Calpains%20mediate%20epithelial-cell%20death%20during%20mammary%20gland%20involution:%20mitochondria%20and%20lysosomal%20destabilization&rft.jtitle=Cell%20death%20and%20differentiation&rft.au=Arnandis,%20T&rft.date=2012-09-01&rft.volume=19&rft.issue=9&rft.spage=1536&rft.epage=1548&rft.pages=1536-1548&rft.issn=1350-9047&rft.eissn=1476-5403&rft_id=info:doi/10.1038/cdd.2012.46&rft_dat=%3Cproquest_pubme%3E1033535014%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1033167113&rft_id=info:pmid/22555453&rfr_iscdi=true |