Endoplasmic reticulum calcium pool depletion-induced apoptosis is coupled with activation of the death receptor 5 pathway
Thapsigargin (TG), by inducing perturbations in cellular Ca(2+) homeostasis, has been shown to induce apoptosis. The molecular mechanisms of Ca(2+) perturbation-induced apoptosis are not fully understood. In this study, we demonstrate for the first time that TG-mediated perturbations in Ca(2+) homeo...
Gespeichert in:
| Veröffentlicht in: | Oncogene 2002-04, Vol.21 (17), p.2623-2633 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2633 |
|---|---|
| container_issue | 17 |
| container_start_page | 2623 |
| container_title | Oncogene |
| container_volume | 21 |
| creator | QIN HE DONG IK LEE RONG RONG MYOUNGHEE YU XIUQUAN LUO KLEIN, Michael EL-DEIRY, Wafik S YING HUANG HUSSAIN, Arif SHEIKH, M. Saeed |
| description | Thapsigargin (TG), by inducing perturbations in cellular Ca(2+) homeostasis, has been shown to induce apoptosis. The molecular mechanisms of Ca(2+) perturbation-induced apoptosis are not fully understood. In this study, we demonstrate for the first time that TG-mediated perturbations in Ca(2+) homeostasis are coupled with activation of the death receptor 5 (DR5)-dependent apoptotic pathway in human cancer cells. TG selectively upregulated DR5 but had no effect on the expression of the other TRAIL receptor, DR4. TG also upregulated the expression of the DR5 ligand TRAIL (tumor necrosis factor-related apoptosis inducing ligand), albeit in a cell-type specific manner. TG-induced apoptosis has been shown to be associated with activation of the mitochondrial pathway. We found that TG upregulation of DR5 and TRAIL was coupled with caspase 8 activation and Bid cleavage, suggesting that the TG-regulated DR5 pathway could be linked to the mitochondrial pathway. TG enhanced not only DR5 mRNA stability but also increased induction of the DR5 genomic promoter-reporter gene. The TG-induced increase in DR5 expression appeared to occur as a consequence of TG-induced endoplasmic reticulum (ER) Ca(2+) pool depletion. Thus, we report our novel findings that ER Ca(2+) pool depletion-induced apoptotic signals are mediated, at least in part, via a DR5-dependent apoptotic pathway and there appears to be a cross-talk between the death receptor and mitochondrial pathways. |
| doi_str_mv | 10.1038/sj.onc.1205345 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_71611581</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A200315757</galeid><sourcerecordid>A200315757</sourcerecordid><originalsourceid>FETCH-LOGICAL-c485t-ccf747ddf9b85410341c3a4f48a6deff0b3248f5a479a6848971184decc0f5c93</originalsourceid><addsrcrecordid>eNp1kt9rFDEQx4Mo9lp99VGCUt_2TDbJZvNYSv0BBV_0OeQmic2xt1mTXcv9987hwoFUEhhm5vOdTJgh5A1nW85E_7Hut3mELW-ZElI9IxsuddcoZeRzsmFGsca0or0gl7XuGWPasPYlueDcdEoJtSHHu9HnaXD1kICWMCdYhuVAwQ2Q0E45D9SHacBMHps0-gWCp27K05xrqhQv5AXznj6m-YE6mNNvd4JpjnR-CKh2GC8BAkoKVXRC_9EdX5EX0Q01vF7tFfnx6e777Zfm_tvnr7c39w3IXs0NQNRSex_NrlcS_yw5CCej7F3nQ4xsJ1rZR-WkNq7rZW805730AYBFBUZckQ9_604l_1pCne0hVQjD4MaQl2o17zhXPUfw_T_gPi9lxN5s20kueNcqhtS7_1KtFtxIYc6lfroh2DTGPBcHp3ftTcuY4EorjdT2CQqPDziNPIaYMP6UAEqutYRop5IOrhwtZ_a0DrbuLa6DXdcBBW_XZpfdIfgzvs4fgesVcBVnHosbIdUzJzolOy7EH4pHvXs</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>227319439</pqid></control><display><type>article</type><title>Endoplasmic reticulum calcium pool depletion-induced apoptosis is coupled with activation of the death receptor 5 pathway</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Nature Journals Online</source><source>SpringerLink Journals - AutoHoldings</source><creator>QIN HE ; DONG IK LEE ; RONG RONG ; MYOUNGHEE YU ; XIUQUAN LUO ; KLEIN, Michael ; EL-DEIRY, Wafik S ; YING HUANG ; HUSSAIN, Arif ; SHEIKH, M. Saeed</creator><creatorcontrib>QIN HE ; DONG IK LEE ; RONG RONG ; MYOUNGHEE YU ; XIUQUAN LUO ; KLEIN, Michael ; EL-DEIRY, Wafik S ; YING HUANG ; HUSSAIN, Arif ; SHEIKH, M. Saeed</creatorcontrib><description>Thapsigargin (TG), by inducing perturbations in cellular Ca(2+) homeostasis, has been shown to induce apoptosis. The molecular mechanisms of Ca(2+) perturbation-induced apoptosis are not fully understood. In this study, we demonstrate for the first time that TG-mediated perturbations in Ca(2+) homeostasis are coupled with activation of the death receptor 5 (DR5)-dependent apoptotic pathway in human cancer cells. TG selectively upregulated DR5 but had no effect on the expression of the other TRAIL receptor, DR4. TG also upregulated the expression of the DR5 ligand TRAIL (tumor necrosis factor-related apoptosis inducing ligand), albeit in a cell-type specific manner. TG-induced apoptosis has been shown to be associated with activation of the mitochondrial pathway. We found that TG upregulation of DR5 and TRAIL was coupled with caspase 8 activation and Bid cleavage, suggesting that the TG-regulated DR5 pathway could be linked to the mitochondrial pathway. TG enhanced not only DR5 mRNA stability but also increased induction of the DR5 genomic promoter-reporter gene. The TG-induced increase in DR5 expression appeared to occur as a consequence of TG-induced endoplasmic reticulum (ER) Ca(2+) pool depletion. Thus, we report our novel findings that ER Ca(2+) pool depletion-induced apoptotic signals are mediated, at least in part, via a DR5-dependent apoptotic pathway and there appears to be a cross-talk between the death receptor and mitochondrial pathways.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1205345</identifier><identifier>PMID: 11965535</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing</publisher><subject>Ageing, cell death ; Apoptosis ; Apoptosis Regulatory Proteins ; Biological and medical sciences ; Blotting, Northern ; Blotting, Western ; Calcium (reticular) ; Calcium - metabolism ; Calcium homeostasis ; Calcium signalling ; Cancer ; Caspase 8 ; Caspase 9 ; Caspases - metabolism ; Cell cycle ; Cell physiology ; Death ; DNA Primers - chemistry ; Endoplasmic reticulum ; Endoplasmic Reticulum - metabolism ; Enzyme Activation ; Female ; Fundamental and applied biological sciences. Psychology ; Homeostasis ; Humans ; Ligands ; Luciferases - metabolism ; Male ; Membrane Glycoproteins - metabolism ; Mitochondria ; Mitochondria - metabolism ; Molecular and cellular biology ; Molecular modelling ; mRNA stability ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; Receptors, Tumor Necrosis Factor - metabolism ; Reporter gene ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; Thapsigargin ; Thapsigargin - pharmacology ; TNF-Related Apoptosis-Inducing Ligand ; TRAIL protein ; Tumor Cells, Cultured - drug effects ; Tumor Cells, Cultured - metabolism ; Tumor Necrosis Factor-alpha - metabolism ; Tumor necrosis factor-TNF ; Up-Regulation</subject><ispartof>Oncogene, 2002-04, Vol.21 (17), p.2623-2633</ispartof><rights>2002 INIST-CNRS</rights><rights>COPYRIGHT 2002 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 18, 2002</rights><rights>Macmillan Publishers Limited 2002.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-ccf747ddf9b85410341c3a4f48a6deff0b3248f5a479a6848971184decc0f5c93</citedby><cites>FETCH-LOGICAL-c485t-ccf747ddf9b85410341c3a4f48a6deff0b3248f5a479a6848971184decc0f5c93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13654613$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11965535$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>QIN HE</creatorcontrib><creatorcontrib>DONG IK LEE</creatorcontrib><creatorcontrib>RONG RONG</creatorcontrib><creatorcontrib>MYOUNGHEE YU</creatorcontrib><creatorcontrib>XIUQUAN LUO</creatorcontrib><creatorcontrib>KLEIN, Michael</creatorcontrib><creatorcontrib>EL-DEIRY, Wafik S</creatorcontrib><creatorcontrib>YING HUANG</creatorcontrib><creatorcontrib>HUSSAIN, Arif</creatorcontrib><creatorcontrib>SHEIKH, M. Saeed</creatorcontrib><title>Endoplasmic reticulum calcium pool depletion-induced apoptosis is coupled with activation of the death receptor 5 pathway</title><title>Oncogene</title><addtitle>Oncogene</addtitle><description>Thapsigargin (TG), by inducing perturbations in cellular Ca(2+) homeostasis, has been shown to induce apoptosis. The molecular mechanisms of Ca(2+) perturbation-induced apoptosis are not fully understood. In this study, we demonstrate for the first time that TG-mediated perturbations in Ca(2+) homeostasis are coupled with activation of the death receptor 5 (DR5)-dependent apoptotic pathway in human cancer cells. TG selectively upregulated DR5 but had no effect on the expression of the other TRAIL receptor, DR4. TG also upregulated the expression of the DR5 ligand TRAIL (tumor necrosis factor-related apoptosis inducing ligand), albeit in a cell-type specific manner. TG-induced apoptosis has been shown to be associated with activation of the mitochondrial pathway. We found that TG upregulation of DR5 and TRAIL was coupled with caspase 8 activation and Bid cleavage, suggesting that the TG-regulated DR5 pathway could be linked to the mitochondrial pathway. TG enhanced not only DR5 mRNA stability but also increased induction of the DR5 genomic promoter-reporter gene. The TG-induced increase in DR5 expression appeared to occur as a consequence of TG-induced endoplasmic reticulum (ER) Ca(2+) pool depletion. Thus, we report our novel findings that ER Ca(2+) pool depletion-induced apoptotic signals are mediated, at least in part, via a DR5-dependent apoptotic pathway and there appears to be a cross-talk between the death receptor and mitochondrial pathways.</description><subject>Ageing, cell death</subject><subject>Apoptosis</subject><subject>Apoptosis Regulatory Proteins</subject><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>Blotting, Western</subject><subject>Calcium (reticular)</subject><subject>Calcium - metabolism</subject><subject>Calcium homeostasis</subject><subject>Calcium signalling</subject><subject>Cancer</subject><subject>Caspase 8</subject><subject>Caspase 9</subject><subject>Caspases - metabolism</subject><subject>Cell cycle</subject><subject>Cell physiology</subject><subject>Death</subject><subject>DNA Primers - chemistry</subject><subject>Endoplasmic reticulum</subject><subject>Endoplasmic Reticulum - metabolism</subject><subject>Enzyme Activation</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Ligands</subject><subject>Luciferases - metabolism</subject><subject>Male</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Mitochondria</subject><subject>Mitochondria - metabolism</subject><subject>Molecular and cellular biology</subject><subject>Molecular modelling</subject><subject>mRNA stability</subject><subject>Receptors, TNF-Related Apoptosis-Inducing Ligand</subject><subject>Receptors, Tumor Necrosis Factor - metabolism</subject><subject>Reporter gene</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - genetics</subject><subject>Thapsigargin</subject><subject>Thapsigargin - pharmacology</subject><subject>TNF-Related Apoptosis-Inducing Ligand</subject><subject>TRAIL protein</subject><subject>Tumor Cells, Cultured - drug effects</subject><subject>Tumor Cells, Cultured - metabolism</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Tumor necrosis factor-TNF</subject><subject>Up-Regulation</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kt9rFDEQx4Mo9lp99VGCUt_2TDbJZvNYSv0BBV_0OeQmic2xt1mTXcv9987hwoFUEhhm5vOdTJgh5A1nW85E_7Hut3mELW-ZElI9IxsuddcoZeRzsmFGsca0or0gl7XuGWPasPYlueDcdEoJtSHHu9HnaXD1kICWMCdYhuVAwQ2Q0E45D9SHacBMHps0-gWCp27K05xrqhQv5AXznj6m-YE6mNNvd4JpjnR-CKh2GC8BAkoKVXRC_9EdX5EX0Q01vF7tFfnx6e777Zfm_tvnr7c39w3IXs0NQNRSex_NrlcS_yw5CCej7F3nQ4xsJ1rZR-WkNq7rZW805730AYBFBUZckQ9_604l_1pCne0hVQjD4MaQl2o17zhXPUfw_T_gPi9lxN5s20kueNcqhtS7_1KtFtxIYc6lfroh2DTGPBcHp3ftTcuY4EorjdT2CQqPDziNPIaYMP6UAEqutYRop5IOrhwtZ_a0DrbuLa6DXdcBBW_XZpfdIfgzvs4fgesVcBVnHosbIdUzJzolOy7EH4pHvXs</recordid><startdate>20020418</startdate><enddate>20020418</enddate><creator>QIN HE</creator><creator>DONG IK LEE</creator><creator>RONG RONG</creator><creator>MYOUNGHEE YU</creator><creator>XIUQUAN LUO</creator><creator>KLEIN, Michael</creator><creator>EL-DEIRY, Wafik S</creator><creator>YING HUANG</creator><creator>HUSSAIN, Arif</creator><creator>SHEIKH, M. Saeed</creator><general>Nature Publishing</general><general>Nature Publishing Group</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>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</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>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20020418</creationdate><title>Endoplasmic reticulum calcium pool depletion-induced apoptosis is coupled with activation of the death receptor 5 pathway</title><author>QIN HE ; DONG IK LEE ; RONG RONG ; MYOUNGHEE YU ; XIUQUAN LUO ; KLEIN, Michael ; EL-DEIRY, Wafik S ; YING HUANG ; HUSSAIN, Arif ; SHEIKH, M. Saeed</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c485t-ccf747ddf9b85410341c3a4f48a6deff0b3248f5a479a6848971184decc0f5c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Ageing, cell death</topic><topic>Apoptosis</topic><topic>Apoptosis Regulatory Proteins</topic><topic>Biological and medical sciences</topic><topic>Blotting, Northern</topic><topic>Blotting, Western</topic><topic>Calcium (reticular)</topic><topic>Calcium - metabolism</topic><topic>Calcium homeostasis</topic><topic>Calcium signalling</topic><topic>Cancer</topic><topic>Caspase 8</topic><topic>Caspase 9</topic><topic>Caspases - metabolism</topic><topic>Cell cycle</topic><topic>Cell physiology</topic><topic>Death</topic><topic>DNA Primers - chemistry</topic><topic>Endoplasmic reticulum</topic><topic>Endoplasmic Reticulum - metabolism</topic><topic>Enzyme Activation</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Ligands</topic><topic>Luciferases - metabolism</topic><topic>Male</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Mitochondria</topic><topic>Mitochondria - metabolism</topic><topic>Molecular and cellular biology</topic><topic>Molecular modelling</topic><topic>mRNA stability</topic><topic>Receptors, TNF-Related Apoptosis-Inducing Ligand</topic><topic>Receptors, Tumor Necrosis Factor - metabolism</topic><topic>Reporter gene</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - genetics</topic><topic>Thapsigargin</topic><topic>Thapsigargin - pharmacology</topic><topic>TNF-Related Apoptosis-Inducing Ligand</topic><topic>TRAIL protein</topic><topic>Tumor Cells, Cultured - drug effects</topic><topic>Tumor Cells, Cultured - metabolism</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Tumor necrosis factor-TNF</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>QIN HE</creatorcontrib><creatorcontrib>DONG IK LEE</creatorcontrib><creatorcontrib>RONG RONG</creatorcontrib><creatorcontrib>MYOUNGHEE YU</creatorcontrib><creatorcontrib>XIUQUAN LUO</creatorcontrib><creatorcontrib>KLEIN, Michael</creatorcontrib><creatorcontrib>EL-DEIRY, Wafik S</creatorcontrib><creatorcontrib>YING HUANG</creatorcontrib><creatorcontrib>HUSSAIN, Arif</creatorcontrib><creatorcontrib>SHEIKH, M. Saeed</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>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS 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>Public Health Database</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>Research Library (Alumni Edition)</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>Research Library Prep</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>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</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>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>QIN HE</au><au>DONG IK LEE</au><au>RONG RONG</au><au>MYOUNGHEE YU</au><au>XIUQUAN LUO</au><au>KLEIN, Michael</au><au>EL-DEIRY, Wafik S</au><au>YING HUANG</au><au>HUSSAIN, Arif</au><au>SHEIKH, M. Saeed</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endoplasmic reticulum calcium pool depletion-induced apoptosis is coupled with activation of the death receptor 5 pathway</atitle><jtitle>Oncogene</jtitle><addtitle>Oncogene</addtitle><date>2002-04-18</date><risdate>2002</risdate><volume>21</volume><issue>17</issue><spage>2623</spage><epage>2633</epage><pages>2623-2633</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Thapsigargin (TG), by inducing perturbations in cellular Ca(2+) homeostasis, has been shown to induce apoptosis. The molecular mechanisms of Ca(2+) perturbation-induced apoptosis are not fully understood. In this study, we demonstrate for the first time that TG-mediated perturbations in Ca(2+) homeostasis are coupled with activation of the death receptor 5 (DR5)-dependent apoptotic pathway in human cancer cells. TG selectively upregulated DR5 but had no effect on the expression of the other TRAIL receptor, DR4. TG also upregulated the expression of the DR5 ligand TRAIL (tumor necrosis factor-related apoptosis inducing ligand), albeit in a cell-type specific manner. TG-induced apoptosis has been shown to be associated with activation of the mitochondrial pathway. We found that TG upregulation of DR5 and TRAIL was coupled with caspase 8 activation and Bid cleavage, suggesting that the TG-regulated DR5 pathway could be linked to the mitochondrial pathway. TG enhanced not only DR5 mRNA stability but also increased induction of the DR5 genomic promoter-reporter gene. The TG-induced increase in DR5 expression appeared to occur as a consequence of TG-induced endoplasmic reticulum (ER) Ca(2+) pool depletion. Thus, we report our novel findings that ER Ca(2+) pool depletion-induced apoptotic signals are mediated, at least in part, via a DR5-dependent apoptotic pathway and there appears to be a cross-talk between the death receptor and mitochondrial pathways.</abstract><cop>Basingstoke</cop><pub>Nature Publishing</pub><pmid>11965535</pmid><doi>10.1038/sj.onc.1205345</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0950-9232 |
| ispartof | Oncogene, 2002-04, Vol.21 (17), p.2623-2633 |
| issn | 0950-9232 1476-5594 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71611581 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | Ageing, cell death Apoptosis Apoptosis Regulatory Proteins Biological and medical sciences Blotting, Northern Blotting, Western Calcium (reticular) Calcium - metabolism Calcium homeostasis Calcium signalling Cancer Caspase 8 Caspase 9 Caspases - metabolism Cell cycle Cell physiology Death DNA Primers - chemistry Endoplasmic reticulum Endoplasmic Reticulum - metabolism Enzyme Activation Female Fundamental and applied biological sciences. Psychology Homeostasis Humans Ligands Luciferases - metabolism Male Membrane Glycoproteins - metabolism Mitochondria Mitochondria - metabolism Molecular and cellular biology Molecular modelling mRNA stability Receptors, TNF-Related Apoptosis-Inducing Ligand Receptors, Tumor Necrosis Factor - metabolism Reporter gene Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - biosynthesis RNA, Messenger - genetics Thapsigargin Thapsigargin - pharmacology TNF-Related Apoptosis-Inducing Ligand TRAIL protein Tumor Cells, Cultured - drug effects Tumor Cells, Cultured - metabolism Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-TNF Up-Regulation |
| title | Endoplasmic reticulum calcium pool depletion-induced apoptosis is coupled with activation of the death receptor 5 pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-11T18%3A04%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Endoplasmic%20reticulum%20calcium%20pool%20depletion-induced%20apoptosis%20is%20coupled%20with%20activation%20of%20the%20death%20receptor%205%20pathway&rft.jtitle=Oncogene&rft.au=QIN%20HE&rft.date=2002-04-18&rft.volume=21&rft.issue=17&rft.spage=2623&rft.epage=2633&rft.pages=2623-2633&rft.issn=0950-9232&rft.eissn=1476-5594&rft.coden=ONCNES&rft_id=info:doi/10.1038/sj.onc.1205345&rft_dat=%3Cgale_proqu%3EA200315757%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=227319439&rft_id=info:pmid/11965535&rft_galeid=A200315757&rfr_iscdi=true |