Caspase Activation and Mitochondrial Cytochrome C Release during Hypoxia-mediated Apoptosis of Adult Ventricular Myocytes
D. de Moissac, R. M. Gurevich, H. Zheng, P. K. Singal and L. A. Kirshenbaum. Caspase Activation and Mitochondrial Cytochrome C Release during Hypoxia-mediated Apoptosis of Adult Ventricular Myocytes. Journal of Molecular and Cellular Cardiology (2000) 32, 53–63. Oxygen deprivation for prolonged peri...
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| creator | Moissac, Danielle de Gurevich, Rhonna M Zheng, Hui Singal, Pawan K Kirshenbaum, Lorrie A |
| description | D. de Moissac, R. M. Gurevich, H. Zheng, P. K. Singal and L. A. Kirshenbaum. Caspase Activation and Mitochondrial Cytochrome C Release during Hypoxia-mediated Apoptosis of Adult Ventricular Myocytes. Journal of Molecular and Cellular Cardiology (2000) 32, 53–63. Oxygen deprivation for prolonged periods leads to cardiac cell death and ventricular dysfunction. The ability to prevent myocardial cell death would be of significant therapeutic value in maintaining cardiac function after injury. While caspases have been suggested to play a critical role in apoptosis, their involvement during hypoxic injury has not been formally determined. In this report, we show that adult ventricular myocytes subjected to hypoxia for 1 h undergo a three-fold increase (P |
| doi_str_mv | 10.1006/jmcc.1999.1057 |
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M. Gurevich, H. Zheng, P. K. Singal and L. A. Kirshenbaum. Caspase Activation and Mitochondrial Cytochrome C Release during Hypoxia-mediated Apoptosis of Adult Ventricular Myocytes. Journal of Molecular and Cellular Cardiology (2000) 32, 53–63. Oxygen deprivation for prolonged periods leads to cardiac cell death and ventricular dysfunction. The ability to prevent myocardial cell death would be of significant therapeutic value in maintaining cardiac function after injury. While caspases have been suggested to play a critical role in apoptosis, their involvement during hypoxic injury has not been formally determined. In this report, we show that adult ventricular myocytes subjected to hypoxia for 1 h undergo a three-fold increase (P<0.05) in the incidence of apoptosis as determined by TUNEL analysis and Hoechst 33258 nuclear staining. Western blot analysis of hypoxic myocytes revealed a 10-fold increase in the proteolytic processing of caspase 3 to p17 with a concomitant cleavage of the caspase 3 substrate PARP from 116 kd to p85 kd compared to normoxic controls. Defects in mitochondrial membrane integrity were also observed as evidenced by the translocation of cytochrome c from the mitochondrial to cytosolic compartment of hypoxic cells. Pretreatment of ventricular myocytes with the peptide-caspase inhibitor known to block caspases related to caspase 1 (Ac-YVAD-CHO) attenuated cytochrome c release, processing of caspase 3, and apoptosis. While the caspase inhibitor (Ac-DEVD-CHO) which blocks caspases related to caspase 3, suppressed the cleavage of PARP and apoptosis, it had no effect on cytochrome c release by mitochondria. The data provide direct evidence for the proteolytic activation of caspases during hypoxia-mediated apoptosis of adult ventricular myocytes. Furthermore, the data suggest a hierarchical scheme for caspase activation with mitochondrial cytochrome c release occurring proximally to DEVD-CHO-inhibitable caspases.</description><identifier>ISSN: 0022-2828</identifier><identifier>EISSN: 1095-8584</identifier><identifier>DOI: 10.1006/jmcc.1999.1057</identifier><identifier>PMID: 10652190</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ventricular myocytes ; Animals ; Apoptosis ; Caspase 3 ; Caspase Inhibitors ; Caspases ; Caspases - metabolism ; Cell Hypoxia ; Cells, Cultured ; Cysteine Proteinase Inhibitors - pharmacology ; Cytochrome c ; Cytochrome c Group - metabolism ; Enzyme Activation ; Heart Ventricles - cytology ; Hypoxia ; Male ; Mitochondria, Heart - enzymology ; Mitochondria, Heart - metabolism ; Oligopeptides - pharmacology ; Rats ; Rats, Sprague-Dawley</subject><ispartof>Journal of molecular and cellular cardiology, 2000-01, Vol.32 (1), p.53-63</ispartof><rights>2000 Academic Press</rights><rights>Copyright 2000 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-d1996c7ceeef82f1fe13a40f83b9615ccc8c80d5e73bb0ef593f972ae225828f3</citedby><cites>FETCH-LOGICAL-c406t-d1996c7ceeef82f1fe13a40f83b9615ccc8c80d5e73bb0ef593f972ae225828f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/jmcc.1999.1057$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10652190$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moissac, Danielle de</creatorcontrib><creatorcontrib>Gurevich, Rhonna M</creatorcontrib><creatorcontrib>Zheng, Hui</creatorcontrib><creatorcontrib>Singal, Pawan K</creatorcontrib><creatorcontrib>Kirshenbaum, Lorrie A</creatorcontrib><title>Caspase Activation and Mitochondrial Cytochrome C Release during Hypoxia-mediated Apoptosis of Adult Ventricular Myocytes</title><title>Journal of molecular and cellular cardiology</title><addtitle>J Mol Cell Cardiol</addtitle><description>D. de Moissac, R. M. Gurevich, H. Zheng, P. K. Singal and L. A. Kirshenbaum. Caspase Activation and Mitochondrial Cytochrome C Release during Hypoxia-mediated Apoptosis of Adult Ventricular Myocytes. Journal of Molecular and Cellular Cardiology (2000) 32, 53–63. Oxygen deprivation for prolonged periods leads to cardiac cell death and ventricular dysfunction. The ability to prevent myocardial cell death would be of significant therapeutic value in maintaining cardiac function after injury. While caspases have been suggested to play a critical role in apoptosis, their involvement during hypoxic injury has not been formally determined. In this report, we show that adult ventricular myocytes subjected to hypoxia for 1 h undergo a three-fold increase (P<0.05) in the incidence of apoptosis as determined by TUNEL analysis and Hoechst 33258 nuclear staining. Western blot analysis of hypoxic myocytes revealed a 10-fold increase in the proteolytic processing of caspase 3 to p17 with a concomitant cleavage of the caspase 3 substrate PARP from 116 kd to p85 kd compared to normoxic controls. Defects in mitochondrial membrane integrity were also observed as evidenced by the translocation of cytochrome c from the mitochondrial to cytosolic compartment of hypoxic cells. Pretreatment of ventricular myocytes with the peptide-caspase inhibitor known to block caspases related to caspase 1 (Ac-YVAD-CHO) attenuated cytochrome c release, processing of caspase 3, and apoptosis. While the caspase inhibitor (Ac-DEVD-CHO) which blocks caspases related to caspase 3, suppressed the cleavage of PARP and apoptosis, it had no effect on cytochrome c release by mitochondria. The data provide direct evidence for the proteolytic activation of caspases during hypoxia-mediated apoptosis of adult ventricular myocytes. Furthermore, the data suggest a hierarchical scheme for caspase activation with mitochondrial cytochrome c release occurring proximally to DEVD-CHO-inhibitable caspases.</description><subject>Adult ventricular myocytes</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Caspase 3</subject><subject>Caspase Inhibitors</subject><subject>Caspases</subject><subject>Caspases - metabolism</subject><subject>Cell Hypoxia</subject><subject>Cells, Cultured</subject><subject>Cysteine Proteinase Inhibitors - pharmacology</subject><subject>Cytochrome c</subject><subject>Cytochrome c Group - metabolism</subject><subject>Enzyme Activation</subject><subject>Heart Ventricles - cytology</subject><subject>Hypoxia</subject><subject>Male</subject><subject>Mitochondria, Heart - enzymology</subject><subject>Mitochondria, Heart - metabolism</subject><subject>Oligopeptides - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><issn>0022-2828</issn><issn>1095-8584</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEFv1DAQhS1ERZfClSPyiVsW29kk9nEV0RapFRICrpZ3PAZXSRxsp2r-fR1tD1w4jUb63pPeR8gHzvacsfbzwwiw50qp8jbdK7LjTDWVbOThNdkxJkQlpJCX5G1KD4wxdajrN-SSs7YRXLEdWXuTZpOQHiH7R5N9mKiZLL33OcCfMNnozUD7dftiGJH29DsOuCXsEv30m96uc3jyphrRepPR0uMc5hySTzQ4erTLkOkvnHL0sAwm0vs1wJoxvSMXzgwJ37_cK_Lz-suP_ra6-3bztT_eVXBgba5sGddCB4jopHDcIa_NgTlZn1TLGwCQIJltsKtPJ4auUbVTnTAoRFOWu_qKfDr3zjH8XTBlPfoEOAxmwrAk3THZtbxTBdyfQYghpYhOz9GPJq6aM73J1ptsvcnWm-wS-PjSvJzK-n_ws90CyDOAZd-jx6gTeJygmIoIWdvg_9f9DA3HkNw</recordid><startdate>200001</startdate><enddate>200001</enddate><creator>Moissac, Danielle de</creator><creator>Gurevich, Rhonna M</creator><creator>Zheng, Hui</creator><creator>Singal, Pawan K</creator><creator>Kirshenbaum, Lorrie A</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>200001</creationdate><title>Caspase Activation and Mitochondrial Cytochrome C Release during Hypoxia-mediated Apoptosis of Adult Ventricular Myocytes</title><author>Moissac, Danielle de ; Gurevich, Rhonna M ; Zheng, Hui ; Singal, Pawan K ; Kirshenbaum, Lorrie A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-d1996c7ceeef82f1fe13a40f83b9615ccc8c80d5e73bb0ef593f972ae225828f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adult ventricular myocytes</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Caspase 3</topic><topic>Caspase Inhibitors</topic><topic>Caspases</topic><topic>Caspases - metabolism</topic><topic>Cell Hypoxia</topic><topic>Cells, Cultured</topic><topic>Cysteine Proteinase Inhibitors - pharmacology</topic><topic>Cytochrome c</topic><topic>Cytochrome c Group - metabolism</topic><topic>Enzyme Activation</topic><topic>Heart Ventricles - cytology</topic><topic>Hypoxia</topic><topic>Male</topic><topic>Mitochondria, Heart - enzymology</topic><topic>Mitochondria, Heart - metabolism</topic><topic>Oligopeptides - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moissac, Danielle de</creatorcontrib><creatorcontrib>Gurevich, Rhonna M</creatorcontrib><creatorcontrib>Zheng, Hui</creatorcontrib><creatorcontrib>Singal, Pawan K</creatorcontrib><creatorcontrib>Kirshenbaum, Lorrie A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of molecular and cellular cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moissac, Danielle de</au><au>Gurevich, Rhonna M</au><au>Zheng, Hui</au><au>Singal, Pawan K</au><au>Kirshenbaum, Lorrie A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Caspase Activation and Mitochondrial Cytochrome C Release during Hypoxia-mediated Apoptosis of Adult Ventricular Myocytes</atitle><jtitle>Journal of molecular and cellular cardiology</jtitle><addtitle>J Mol Cell Cardiol</addtitle><date>2000-01</date><risdate>2000</risdate><volume>32</volume><issue>1</issue><spage>53</spage><epage>63</epage><pages>53-63</pages><issn>0022-2828</issn><eissn>1095-8584</eissn><abstract>D. de Moissac, R. M. Gurevich, H. Zheng, P. K. Singal and L. A. Kirshenbaum. Caspase Activation and Mitochondrial Cytochrome C Release during Hypoxia-mediated Apoptosis of Adult Ventricular Myocytes. Journal of Molecular and Cellular Cardiology (2000) 32, 53–63. Oxygen deprivation for prolonged periods leads to cardiac cell death and ventricular dysfunction. The ability to prevent myocardial cell death would be of significant therapeutic value in maintaining cardiac function after injury. While caspases have been suggested to play a critical role in apoptosis, their involvement during hypoxic injury has not been formally determined. In this report, we show that adult ventricular myocytes subjected to hypoxia for 1 h undergo a three-fold increase (P<0.05) in the incidence of apoptosis as determined by TUNEL analysis and Hoechst 33258 nuclear staining. Western blot analysis of hypoxic myocytes revealed a 10-fold increase in the proteolytic processing of caspase 3 to p17 with a concomitant cleavage of the caspase 3 substrate PARP from 116 kd to p85 kd compared to normoxic controls. Defects in mitochondrial membrane integrity were also observed as evidenced by the translocation of cytochrome c from the mitochondrial to cytosolic compartment of hypoxic cells. Pretreatment of ventricular myocytes with the peptide-caspase inhibitor known to block caspases related to caspase 1 (Ac-YVAD-CHO) attenuated cytochrome c release, processing of caspase 3, and apoptosis. While the caspase inhibitor (Ac-DEVD-CHO) which blocks caspases related to caspase 3, suppressed the cleavage of PARP and apoptosis, it had no effect on cytochrome c release by mitochondria. The data provide direct evidence for the proteolytic activation of caspases during hypoxia-mediated apoptosis of adult ventricular myocytes. Furthermore, the data suggest a hierarchical scheme for caspase activation with mitochondrial cytochrome c release occurring proximally to DEVD-CHO-inhibitable caspases.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>10652190</pmid><doi>10.1006/jmcc.1999.1057</doi><tpages>11</tpages></addata></record> |
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| subjects | Adult ventricular myocytes Animals Apoptosis Caspase 3 Caspase Inhibitors Caspases Caspases - metabolism Cell Hypoxia Cells, Cultured Cysteine Proteinase Inhibitors - pharmacology Cytochrome c Cytochrome c Group - metabolism Enzyme Activation Heart Ventricles - cytology Hypoxia Male Mitochondria, Heart - enzymology Mitochondria, Heart - metabolism Oligopeptides - pharmacology Rats Rats, Sprague-Dawley |
| title | Caspase Activation and Mitochondrial Cytochrome C Release during Hypoxia-mediated Apoptosis of Adult Ventricular Myocytes |
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