Changes in Endoplasmic Reticulum Luminal Environment Affect Cell Sensitivity to Apoptosis
To test the role of ER luminal environment in apoptosis, we generated HeLa cell lines inducible with respect to calreticulin and calnexin and investigated their sensitivity to drug-dependent apoptosis. Overexpression of calreticulin, an ER luminal protein, resulted in an increased sensitivity of the...
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| Veröffentlicht in: | The Journal of cell biology 2000-08, Vol.150 (4), p.731-740 |
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| creator | Nakamura, Kimitoshi Bossy-Wetzel, Ella Burns, Kimberly Fadel, Marc P. Lozyk, Mira Goping, Ing Swie Opas, Michal Bleackley, R. Chris Green, Douglas R. Michalak, Marek |
| description | To test the role of ER luminal environment in apoptosis, we generated HeLa cell lines inducible with respect to calreticulin and calnexin and investigated their sensitivity to drug-dependent apoptosis. Overexpression of calreticulin, an ER luminal protein, resulted in an increased sensitivity of the cells to both thapsigargin- and staurosporine-induced apoptosis. This correlated with an increased release of cytochrome c from the mitochondria. Overexpression of calnexin, an integral ER membrane protein, had no significant effect on drug-induced apoptosis. In contrast, calreticulin-deficient cells were significantly resistant to apoptosis and this resistance correlated with a decreased release of cytochrome c from mitochondria and low levels of caspase 3 activity. This work indicates that changes in the lumen of the ER amplify the release of cytochrome c from mitochondria, and increase caspase activity, during drug-induced apoptosis. There may be communication between the ER and mitochondria, which may involve Ca2+and play an important role in conferring cell sensitivity to apoptosis. Apoptosis may depend on both the presence of external apoptosis-activating signals, and, as shown in this study, on an internal factor represented by the ER. |
| doi_str_mv | 10.1083/jcb.150.4.731 |
| format | Article |
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Chris ; Green, Douglas R. ; Michalak, Marek</creator><creatorcontrib>Nakamura, Kimitoshi ; Bossy-Wetzel, Ella ; Burns, Kimberly ; Fadel, Marc P. ; Lozyk, Mira ; Goping, Ing Swie ; Opas, Michal ; Bleackley, R. Chris ; Green, Douglas R. ; Michalak, Marek</creatorcontrib><description>To test the role of ER luminal environment in apoptosis, we generated HeLa cell lines inducible with respect to calreticulin and calnexin and investigated their sensitivity to drug-dependent apoptosis. Overexpression of calreticulin, an ER luminal protein, resulted in an increased sensitivity of the cells to both thapsigargin- and staurosporine-induced apoptosis. This correlated with an increased release of cytochrome c from the mitochondria. Overexpression of calnexin, an integral ER membrane protein, had no significant effect on drug-induced apoptosis. In contrast, calreticulin-deficient cells were significantly resistant to apoptosis and this resistance correlated with a decreased release of cytochrome c from mitochondria and low levels of caspase 3 activity. This work indicates that changes in the lumen of the ER amplify the release of cytochrome c from mitochondria, and increase caspase activity, during drug-induced apoptosis. There may be communication between the ER and mitochondria, which may involve Ca2+and play an important role in conferring cell sensitivity to apoptosis. Apoptosis may depend on both the presence of external apoptosis-activating signals, and, as shown in this study, on an internal factor represented by the ER.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.150.4.731</identifier><identifier>PMID: 10952999</identifier><identifier>CODEN: JCLBA3</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Animals ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - physiology ; Apoptosis - radiation effects ; Calcium - metabolism ; Calcium-Binding Proteins - genetics ; Calcium-Binding Proteins - physiology ; Calnexin ; Calreticulin ; Cell Line ; Cell lines ; Cells ; Cellular biology ; Cloning, Molecular ; Cytochrome c Group - analysis ; Cytochromes ; Dendritic cells ; Dogs ; Endoplasmic reticulum ; Endoplasmic Reticulum - physiology ; Endoplasmic Reticulum - ultrastructure ; Etoposide - pharmacology ; HeLa Cells ; Homeostasis ; Humans ; Membrane Proteins - physiology ; Mice ; Mitochondria ; Mitochondria - physiology ; Molecular Chaperones - physiology ; Original ; Proteins ; Rabbits ; Ribonucleoproteins - genetics ; Ribonucleoproteins - physiology ; Staurosporine - pharmacology ; T lymphocytes ; Thapsigargin - pharmacology ; Ultraviolet Rays</subject><ispartof>The Journal of cell biology, 2000-08, Vol.150 (4), p.731-740</ispartof><rights>Copyright 2000 The Rockefeller University Press</rights><rights>Copyright Rockefeller University Press Aug 21, 2000</rights><rights>2000 The Rockefeller University Press 2000 The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c497t-c3a3bca0df4cd27759afce9c72be99b495497e53511da56a04c7198036bc72523</citedby><cites>FETCH-LOGICAL-c497t-c3a3bca0df4cd27759afce9c72be99b495497e53511da56a04c7198036bc72523</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10952999$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nakamura, Kimitoshi</creatorcontrib><creatorcontrib>Bossy-Wetzel, Ella</creatorcontrib><creatorcontrib>Burns, Kimberly</creatorcontrib><creatorcontrib>Fadel, Marc P.</creatorcontrib><creatorcontrib>Lozyk, Mira</creatorcontrib><creatorcontrib>Goping, Ing Swie</creatorcontrib><creatorcontrib>Opas, Michal</creatorcontrib><creatorcontrib>Bleackley, R. Chris</creatorcontrib><creatorcontrib>Green, Douglas R.</creatorcontrib><creatorcontrib>Michalak, Marek</creatorcontrib><title>Changes in Endoplasmic Reticulum Luminal Environment Affect Cell Sensitivity to Apoptosis</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>To test the role of ER luminal environment in apoptosis, we generated HeLa cell lines inducible with respect to calreticulin and calnexin and investigated their sensitivity to drug-dependent apoptosis. Overexpression of calreticulin, an ER luminal protein, resulted in an increased sensitivity of the cells to both thapsigargin- and staurosporine-induced apoptosis. This correlated with an increased release of cytochrome c from the mitochondria. Overexpression of calnexin, an integral ER membrane protein, had no significant effect on drug-induced apoptosis. In contrast, calreticulin-deficient cells were significantly resistant to apoptosis and this resistance correlated with a decreased release of cytochrome c from mitochondria and low levels of caspase 3 activity. This work indicates that changes in the lumen of the ER amplify the release of cytochrome c from mitochondria, and increase caspase activity, during drug-induced apoptosis. There may be communication between the ER and mitochondria, which may involve Ca2+and play an important role in conferring cell sensitivity to apoptosis. Apoptosis may depend on both the presence of external apoptosis-activating signals, and, as shown in this study, on an internal factor represented by the ER.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>Apoptosis - radiation effects</subject><subject>Calcium - metabolism</subject><subject>Calcium-Binding Proteins - genetics</subject><subject>Calcium-Binding Proteins - physiology</subject><subject>Calnexin</subject><subject>Calreticulin</subject><subject>Cell Line</subject><subject>Cell lines</subject><subject>Cells</subject><subject>Cellular biology</subject><subject>Cloning, Molecular</subject><subject>Cytochrome c Group - analysis</subject><subject>Cytochromes</subject><subject>Dendritic cells</subject><subject>Dogs</subject><subject>Endoplasmic reticulum</subject><subject>Endoplasmic Reticulum - physiology</subject><subject>Endoplasmic Reticulum - ultrastructure</subject><subject>Etoposide - pharmacology</subject><subject>HeLa Cells</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Membrane Proteins - physiology</subject><subject>Mice</subject><subject>Mitochondria</subject><subject>Mitochondria - physiology</subject><subject>Molecular Chaperones - physiology</subject><subject>Original</subject><subject>Proteins</subject><subject>Rabbits</subject><subject>Ribonucleoproteins - genetics</subject><subject>Ribonucleoproteins - physiology</subject><subject>Staurosporine - pharmacology</subject><subject>T lymphocytes</subject><subject>Thapsigargin - pharmacology</subject><subject>Ultraviolet Rays</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc9rFDEYhoModq0evYkED73N-uXXZnIRlqVVYaFQ9eApZDKZNstMMiaZhf73pmzR6imQ9-HlTR6E3hJYE2jZx4Pt1kTAmq8lI8_QiggOTUs4PEcrAEoaJag4Q69yPgAAl5y9RGcE6q1SaoV-7u5MuHUZ-4AvQx_n0eTJW3zjirfLuEx4v0w-mLGmR59imFwoeDsMzha8c-OIv7mQffFHX-5xiXg7x7nE7PNr9GIwY3ZvHs9z9OPq8vvuS7O__vx1t903litZGssM66yBfuC2p1IKZQbrlJW0c0p1XImKOcEEIb0RGwPcSqJaYJuuMoKyc_Tp1Dsv3eR6W_clM-o5-cmkex2N1_8mwd_p23jUlEhB27YWXDwWpPhrcbnoyWdbn2aCi0vWklIQjKsKfvgPPMQl1b_JD10gactZhZoTZFPMObnhzxIC-sGYrsZ0Naa5rsYq__7p_Cf0SVEF3p2AQy4x_c03FEAI9hvWbJx-</recordid><startdate>20000821</startdate><enddate>20000821</enddate><creator>Nakamura, Kimitoshi</creator><creator>Bossy-Wetzel, Ella</creator><creator>Burns, Kimberly</creator><creator>Fadel, Marc P.</creator><creator>Lozyk, Mira</creator><creator>Goping, Ing Swie</creator><creator>Opas, Michal</creator><creator>Bleackley, R. Chris</creator><creator>Green, Douglas R.</creator><creator>Michalak, Marek</creator><general>Rockefeller University Press</general><general>The Rockefeller University Press</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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20000821</creationdate><title>Changes in Endoplasmic Reticulum Luminal Environment Affect Cell Sensitivity to Apoptosis</title><author>Nakamura, Kimitoshi ; Bossy-Wetzel, Ella ; Burns, Kimberly ; Fadel, Marc P. ; Lozyk, Mira ; Goping, Ing Swie ; Opas, Michal ; Bleackley, R. 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Chris</au><au>Green, Douglas R.</au><au>Michalak, Marek</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Changes in Endoplasmic Reticulum Luminal Environment Affect Cell Sensitivity to Apoptosis</atitle><jtitle>The Journal of cell biology</jtitle><addtitle>J Cell Biol</addtitle><date>2000-08-21</date><risdate>2000</risdate><volume>150</volume><issue>4</issue><spage>731</spage><epage>740</epage><pages>731-740</pages><issn>0021-9525</issn><eissn>1540-8140</eissn><coden>JCLBA3</coden><abstract>To test the role of ER luminal environment in apoptosis, we generated HeLa cell lines inducible with respect to calreticulin and calnexin and investigated their sensitivity to drug-dependent apoptosis. Overexpression of calreticulin, an ER luminal protein, resulted in an increased sensitivity of the cells to both thapsigargin- and staurosporine-induced apoptosis. This correlated with an increased release of cytochrome c from the mitochondria. Overexpression of calnexin, an integral ER membrane protein, had no significant effect on drug-induced apoptosis. In contrast, calreticulin-deficient cells were significantly resistant to apoptosis and this resistance correlated with a decreased release of cytochrome c from mitochondria and low levels of caspase 3 activity. This work indicates that changes in the lumen of the ER amplify the release of cytochrome c from mitochondria, and increase caspase activity, during drug-induced apoptosis. There may be communication between the ER and mitochondria, which may involve Ca2+and play an important role in conferring cell sensitivity to apoptosis. Apoptosis may depend on both the presence of external apoptosis-activating signals, and, as shown in this study, on an internal factor represented by the ER.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>10952999</pmid><doi>10.1083/jcb.150.4.731</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Apoptosis Apoptosis - drug effects Apoptosis - physiology Apoptosis - radiation effects Calcium - metabolism Calcium-Binding Proteins - genetics Calcium-Binding Proteins - physiology Calnexin Calreticulin Cell Line Cell lines Cells Cellular biology Cloning, Molecular Cytochrome c Group - analysis Cytochromes Dendritic cells Dogs Endoplasmic reticulum Endoplasmic Reticulum - physiology Endoplasmic Reticulum - ultrastructure Etoposide - pharmacology HeLa Cells Homeostasis Humans Membrane Proteins - physiology Mice Mitochondria Mitochondria - physiology Molecular Chaperones - physiology Original Proteins Rabbits Ribonucleoproteins - genetics Ribonucleoproteins - physiology Staurosporine - pharmacology T lymphocytes Thapsigargin - pharmacology Ultraviolet Rays |
| title | Changes in Endoplasmic Reticulum Luminal Environment Affect Cell Sensitivity to Apoptosis |
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