Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion
Divisions of 1 Cardiology, 2 Clinical Pharmacology, and 3 Pharmacology, Department of Medicine, Case Western Reserve University and Medical Service, 4 Louis Stokes Veterans Affairs Medical Center, Cleveland, Ohio; Departments of 5 Anesthesiology and 6 Physiology, 7 Cardiovascular Research Center, Me...
Gespeichert in:
Veröffentlicht in: | American Journal of Physiology: Cell Physiology 2007-01, Vol.292 (1), p.C137-C147 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | C147 |
---|---|
container_issue | 1 |
container_start_page | C137 |
container_title | American Journal of Physiology: Cell Physiology |
container_volume | 292 |
creator | Chen, Qun Camara, Amadou K. S Stowe, David F Hoppel, Charles L Lesnefsky, Edward J |
description | Divisions of 1 Cardiology, 2 Clinical Pharmacology, and 3 Pharmacology, Department of Medicine, Case Western Reserve University and Medical Service, 4 Louis Stokes Veterans Affairs Medical Center, Cleveland, Ohio; Departments of 5 Anesthesiology and 6 Physiology, 7 Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee; 8 Zablocki Veterans Affairs Medical Center, Milwaukee; and 9 Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin
Submitted 16 May 2006
; accepted in final form 7 September 2006
Mitochondria are increasingly recognized as lynchpins in the evolution of cardiac injury during ischemia and reperfusion. This review addresses the emerging concept that modulation of mitochondrial respiration during and immediately following an episode of ischemia can attenuate the extent of myocardial injury. The blockade of electron transport and the partial uncoupling of respiration are two mechanisms whereby manipulation of mitochondrial metabolism during ischemia decreases cardiac injury. Although protection by inhibition of electron transport or uncoupling of respiration initially appears to be counterintuitive, the continuation of mitochondrial oxidative phosphorylation in the pathological milieu of ischemia generates reactive oxygen species, mitochondrial calcium overload, and the release of cytochrome c . The initial target of these deleterious mitochondrial-driven processes is the mitochondria themselves. Consequences to the cardiomyocyte, in turn, include oxidative damage, the onset of mitochondrial permeability transition, and activation of apoptotic cascades, all favoring cardiomyocyte death. Ischemia-induced mitochondrial damage carried forward into reperfusion further amplifies these mechanisms of mitochondrial-driven myocyte injury. Interruption of mitochondrial respiration during early reperfusion by pharmacologic blockade of electron transport or even recurrent hypoxia or brief ischemia paradoxically decreases cardiac injury. It increasingly appears that the cardioprotective paradigms of ischemic preconditioning and postconditioning utilize modulation of mitochondrial oxidative metabolism as a key effector mechanism. The initially counterintuitive approach to inhibit mitochondrial respiration provides a new cardioprotective paradigm to decrease cellular injury during both ischemia and reperfusion.
cardiolipin; cytochrome c ; complex I; cytochrome oxidase
Address for reprint requests and other correspond |
doi_str_mv | 10.1152/ajpcell.00270.2006 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1152_ajpcell_00270_2006</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>68417179</sourcerecordid><originalsourceid>FETCH-LOGICAL-c482t-f0442297d1c36b286a60ed70576728a07ef00e251a1c615bb9e3d0eee1fa82113</originalsourceid><addsrcrecordid>eNp1kTGP1DAQhS0E4paDP0CBLAq6LGM7sZMSrThAOkRz1JbXnmy8SuJgJ4I0_HZ8bOAkJKqxxt97Hs8j5CWDPWMVf2vOk8W-3wNwBXsOIB-RXb7gBaukeEx2IKQoJCvFFXmW0hkASi6bp-SKyUaxsql35Ofn4JbezD6MNLQUe7RzzOc5mjFNIc50imHOzUStic4bSwc_B9uF0UVvqBkddWgjmoSJDmu4UD3143mJK3VL9OOJ-mQ7HDY-4oSxXVJ-8zl50po-4YutXpOvN-_vDh-L2y8fPh3e3Ra2rPlctFCWnDfKMSvkkdfSSECnoFJS8dqAwhYAecUMs5JVx2ODwgEistbUnDFxTd5cfPNvvi2YZj3kkfLyzIhhSVrWJVNMNRl8_Q94Dksc82yaCxAlb4TIEL9ANoaUIrZ6in4wcdUM9H00eotG_45G30eTRa825-U4oHuQbFlkoLgAnT91331EPXVrXlIfTutfQ95wzfSBCZX55v_8zdL3d_hj_iN80OnJteIXVdqzMQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>230342933</pqid></control><display><type>article</type><title>Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion</title><source>MEDLINE</source><source>American Physiological Society Paid</source><source>EZB Electronic Journals Library</source><creator>Chen, Qun ; Camara, Amadou K. S ; Stowe, David F ; Hoppel, Charles L ; Lesnefsky, Edward J</creator><creatorcontrib>Chen, Qun ; Camara, Amadou K. S ; Stowe, David F ; Hoppel, Charles L ; Lesnefsky, Edward J</creatorcontrib><description>Divisions of 1 Cardiology, 2 Clinical Pharmacology, and 3 Pharmacology, Department of Medicine, Case Western Reserve University and Medical Service, 4 Louis Stokes Veterans Affairs Medical Center, Cleveland, Ohio; Departments of 5 Anesthesiology and 6 Physiology, 7 Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee; 8 Zablocki Veterans Affairs Medical Center, Milwaukee; and 9 Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin
Submitted 16 May 2006
; accepted in final form 7 September 2006
Mitochondria are increasingly recognized as lynchpins in the evolution of cardiac injury during ischemia and reperfusion. This review addresses the emerging concept that modulation of mitochondrial respiration during and immediately following an episode of ischemia can attenuate the extent of myocardial injury. The blockade of electron transport and the partial uncoupling of respiration are two mechanisms whereby manipulation of mitochondrial metabolism during ischemia decreases cardiac injury. Although protection by inhibition of electron transport or uncoupling of respiration initially appears to be counterintuitive, the continuation of mitochondrial oxidative phosphorylation in the pathological milieu of ischemia generates reactive oxygen species, mitochondrial calcium overload, and the release of cytochrome c . The initial target of these deleterious mitochondrial-driven processes is the mitochondria themselves. Consequences to the cardiomyocyte, in turn, include oxidative damage, the onset of mitochondrial permeability transition, and activation of apoptotic cascades, all favoring cardiomyocyte death. Ischemia-induced mitochondrial damage carried forward into reperfusion further amplifies these mechanisms of mitochondrial-driven myocyte injury. Interruption of mitochondrial respiration during early reperfusion by pharmacologic blockade of electron transport or even recurrent hypoxia or brief ischemia paradoxically decreases cardiac injury. It increasingly appears that the cardioprotective paradigms of ischemic preconditioning and postconditioning utilize modulation of mitochondrial oxidative metabolism as a key effector mechanism. The initially counterintuitive approach to inhibit mitochondrial respiration provides a new cardioprotective paradigm to decrease cellular injury during both ischemia and reperfusion.
cardiolipin; cytochrome c ; complex I; cytochrome oxidase
Address for reprint requests and other correspondence: E. J. Lesnefsky, Cardiology Section, Medical Service 111(W), Louis Stokes VA Medical Center, 10701 East Blvd., Cleveland, OH 44106 (e-mail: EXL9{at}cwru.edu )</description><identifier>ISSN: 0363-6143</identifier><identifier>EISSN: 1522-1563</identifier><identifier>DOI: 10.1152/ajpcell.00270.2006</identifier><identifier>PMID: 16971498</identifier><identifier>CODEN: AJPCDD</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Aging ; Anemia ; Animals ; Cells ; Electron transfer ; Electron Transport ; Enzymes ; Humans ; Ischemic Preconditioning, Myocardial ; Mitochondria, Heart - metabolism ; Myocardial Reperfusion Injury - metabolism ; Myocardial Reperfusion Injury - pathology ; Oxidative Phosphorylation ; Protons ; Reactive Oxygen Species - metabolism</subject><ispartof>American Journal of Physiology: Cell Physiology, 2007-01, Vol.292 (1), p.C137-C147</ispartof><rights>Copyright American Physiological Society Jan 2007</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c482t-f0442297d1c36b286a60ed70576728a07ef00e251a1c615bb9e3d0eee1fa82113</citedby><cites>FETCH-LOGICAL-c482t-f0442297d1c36b286a60ed70576728a07ef00e251a1c615bb9e3d0eee1fa82113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3039,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16971498$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Qun</creatorcontrib><creatorcontrib>Camara, Amadou K. S</creatorcontrib><creatorcontrib>Stowe, David F</creatorcontrib><creatorcontrib>Hoppel, Charles L</creatorcontrib><creatorcontrib>Lesnefsky, Edward J</creatorcontrib><title>Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion</title><title>American Journal of Physiology: Cell Physiology</title><addtitle>Am J Physiol Cell Physiol</addtitle><description>Divisions of 1 Cardiology, 2 Clinical Pharmacology, and 3 Pharmacology, Department of Medicine, Case Western Reserve University and Medical Service, 4 Louis Stokes Veterans Affairs Medical Center, Cleveland, Ohio; Departments of 5 Anesthesiology and 6 Physiology, 7 Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee; 8 Zablocki Veterans Affairs Medical Center, Milwaukee; and 9 Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin
Submitted 16 May 2006
; accepted in final form 7 September 2006
Mitochondria are increasingly recognized as lynchpins in the evolution of cardiac injury during ischemia and reperfusion. This review addresses the emerging concept that modulation of mitochondrial respiration during and immediately following an episode of ischemia can attenuate the extent of myocardial injury. The blockade of electron transport and the partial uncoupling of respiration are two mechanisms whereby manipulation of mitochondrial metabolism during ischemia decreases cardiac injury. Although protection by inhibition of electron transport or uncoupling of respiration initially appears to be counterintuitive, the continuation of mitochondrial oxidative phosphorylation in the pathological milieu of ischemia generates reactive oxygen species, mitochondrial calcium overload, and the release of cytochrome c . The initial target of these deleterious mitochondrial-driven processes is the mitochondria themselves. Consequences to the cardiomyocyte, in turn, include oxidative damage, the onset of mitochondrial permeability transition, and activation of apoptotic cascades, all favoring cardiomyocyte death. Ischemia-induced mitochondrial damage carried forward into reperfusion further amplifies these mechanisms of mitochondrial-driven myocyte injury. Interruption of mitochondrial respiration during early reperfusion by pharmacologic blockade of electron transport or even recurrent hypoxia or brief ischemia paradoxically decreases cardiac injury. It increasingly appears that the cardioprotective paradigms of ischemic preconditioning and postconditioning utilize modulation of mitochondrial oxidative metabolism as a key effector mechanism. The initially counterintuitive approach to inhibit mitochondrial respiration provides a new cardioprotective paradigm to decrease cellular injury during both ischemia and reperfusion.
cardiolipin; cytochrome c ; complex I; cytochrome oxidase
Address for reprint requests and other correspondence: E. J. Lesnefsky, Cardiology Section, Medical Service 111(W), Louis Stokes VA Medical Center, 10701 East Blvd., Cleveland, OH 44106 (e-mail: EXL9{at}cwru.edu )</description><subject>Aging</subject><subject>Anemia</subject><subject>Animals</subject><subject>Cells</subject><subject>Electron transfer</subject><subject>Electron Transport</subject><subject>Enzymes</subject><subject>Humans</subject><subject>Ischemic Preconditioning, Myocardial</subject><subject>Mitochondria, Heart - metabolism</subject><subject>Myocardial Reperfusion Injury - metabolism</subject><subject>Myocardial Reperfusion Injury - pathology</subject><subject>Oxidative Phosphorylation</subject><subject>Protons</subject><subject>Reactive Oxygen Species - metabolism</subject><issn>0363-6143</issn><issn>1522-1563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kTGP1DAQhS0E4paDP0CBLAq6LGM7sZMSrThAOkRz1JbXnmy8SuJgJ4I0_HZ8bOAkJKqxxt97Hs8j5CWDPWMVf2vOk8W-3wNwBXsOIB-RXb7gBaukeEx2IKQoJCvFFXmW0hkASi6bp-SKyUaxsql35Ofn4JbezD6MNLQUe7RzzOc5mjFNIc50imHOzUStic4bSwc_B9uF0UVvqBkddWgjmoSJDmu4UD3143mJK3VL9OOJ-mQ7HDY-4oSxXVJ-8zl50po-4YutXpOvN-_vDh-L2y8fPh3e3Ra2rPlctFCWnDfKMSvkkdfSSECnoFJS8dqAwhYAecUMs5JVx2ODwgEistbUnDFxTd5cfPNvvi2YZj3kkfLyzIhhSVrWJVNMNRl8_Q94Dksc82yaCxAlb4TIEL9ANoaUIrZ6in4wcdUM9H00eotG_45G30eTRa825-U4oHuQbFlkoLgAnT91331EPXVrXlIfTutfQ95wzfSBCZX55v_8zdL3d_hj_iN80OnJteIXVdqzMQ</recordid><startdate>20070101</startdate><enddate>20070101</enddate><creator>Chen, Qun</creator><creator>Camara, Amadou K. S</creator><creator>Stowe, David F</creator><creator>Hoppel, Charles L</creator><creator>Lesnefsky, Edward J</creator><general>American Physiological Society</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>7QP</scope><scope>7TS</scope><scope>7X8</scope></search><sort><creationdate>20070101</creationdate><title>Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion</title><author>Chen, Qun ; Camara, Amadou K. S ; Stowe, David F ; Hoppel, Charles L ; Lesnefsky, Edward J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c482t-f0442297d1c36b286a60ed70576728a07ef00e251a1c615bb9e3d0eee1fa82113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Aging</topic><topic>Anemia</topic><topic>Animals</topic><topic>Cells</topic><topic>Electron transfer</topic><topic>Electron Transport</topic><topic>Enzymes</topic><topic>Humans</topic><topic>Ischemic Preconditioning, Myocardial</topic><topic>Mitochondria, Heart - metabolism</topic><topic>Myocardial Reperfusion Injury - metabolism</topic><topic>Myocardial Reperfusion Injury - pathology</topic><topic>Oxidative Phosphorylation</topic><topic>Protons</topic><topic>Reactive Oxygen Species - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Qun</creatorcontrib><creatorcontrib>Camara, Amadou K. S</creatorcontrib><creatorcontrib>Stowe, David F</creatorcontrib><creatorcontrib>Hoppel, Charles L</creatorcontrib><creatorcontrib>Lesnefsky, Edward J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Physical Education Index</collection><collection>MEDLINE - Academic</collection><jtitle>American Journal of Physiology: Cell Physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Qun</au><au>Camara, Amadou K. S</au><au>Stowe, David F</au><au>Hoppel, Charles L</au><au>Lesnefsky, Edward J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion</atitle><jtitle>American Journal of Physiology: Cell Physiology</jtitle><addtitle>Am J Physiol Cell Physiol</addtitle><date>2007-01-01</date><risdate>2007</risdate><volume>292</volume><issue>1</issue><spage>C137</spage><epage>C147</epage><pages>C137-C147</pages><issn>0363-6143</issn><eissn>1522-1563</eissn><coden>AJPCDD</coden><abstract>Divisions of 1 Cardiology, 2 Clinical Pharmacology, and 3 Pharmacology, Department of Medicine, Case Western Reserve University and Medical Service, 4 Louis Stokes Veterans Affairs Medical Center, Cleveland, Ohio; Departments of 5 Anesthesiology and 6 Physiology, 7 Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee; 8 Zablocki Veterans Affairs Medical Center, Milwaukee; and 9 Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin
Submitted 16 May 2006
; accepted in final form 7 September 2006
Mitochondria are increasingly recognized as lynchpins in the evolution of cardiac injury during ischemia and reperfusion. This review addresses the emerging concept that modulation of mitochondrial respiration during and immediately following an episode of ischemia can attenuate the extent of myocardial injury. The blockade of electron transport and the partial uncoupling of respiration are two mechanisms whereby manipulation of mitochondrial metabolism during ischemia decreases cardiac injury. Although protection by inhibition of electron transport or uncoupling of respiration initially appears to be counterintuitive, the continuation of mitochondrial oxidative phosphorylation in the pathological milieu of ischemia generates reactive oxygen species, mitochondrial calcium overload, and the release of cytochrome c . The initial target of these deleterious mitochondrial-driven processes is the mitochondria themselves. Consequences to the cardiomyocyte, in turn, include oxidative damage, the onset of mitochondrial permeability transition, and activation of apoptotic cascades, all favoring cardiomyocyte death. Ischemia-induced mitochondrial damage carried forward into reperfusion further amplifies these mechanisms of mitochondrial-driven myocyte injury. Interruption of mitochondrial respiration during early reperfusion by pharmacologic blockade of electron transport or even recurrent hypoxia or brief ischemia paradoxically decreases cardiac injury. It increasingly appears that the cardioprotective paradigms of ischemic preconditioning and postconditioning utilize modulation of mitochondrial oxidative metabolism as a key effector mechanism. The initially counterintuitive approach to inhibit mitochondrial respiration provides a new cardioprotective paradigm to decrease cellular injury during both ischemia and reperfusion.
cardiolipin; cytochrome c ; complex I; cytochrome oxidase
Address for reprint requests and other correspondence: E. J. Lesnefsky, Cardiology Section, Medical Service 111(W), Louis Stokes VA Medical Center, 10701 East Blvd., Cleveland, OH 44106 (e-mail: EXL9{at}cwru.edu )</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>16971498</pmid><doi>10.1152/ajpcell.00270.2006</doi></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0363-6143 |
ispartof | American Journal of Physiology: Cell Physiology, 2007-01, Vol.292 (1), p.C137-C147 |
issn | 0363-6143 1522-1563 |
language | eng |
recordid | cdi_crossref_primary_10_1152_ajpcell_00270_2006 |
source | MEDLINE; American Physiological Society Paid; EZB Electronic Journals Library |
subjects | Aging Anemia Animals Cells Electron transfer Electron Transport Enzymes Humans Ischemic Preconditioning, Myocardial Mitochondria, Heart - metabolism Myocardial Reperfusion Injury - metabolism Myocardial Reperfusion Injury - pathology Oxidative Phosphorylation Protons Reactive Oxygen Species - metabolism |
title | Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T05%3A54%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Modulation%20of%20electron%20transport%20protects%20cardiac%20mitochondria%20and%20decreases%20myocardial%20injury%20during%20ischemia%20and%20reperfusion&rft.jtitle=American%20Journal%20of%20Physiology:%20Cell%20Physiology&rft.au=Chen,%20Qun&rft.date=2007-01-01&rft.volume=292&rft.issue=1&rft.spage=C137&rft.epage=C147&rft.pages=C137-C147&rft.issn=0363-6143&rft.eissn=1522-1563&rft.coden=AJPCDD&rft_id=info:doi/10.1152/ajpcell.00270.2006&rft_dat=%3Cproquest_cross%3E68417179%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=230342933&rft_id=info:pmid/16971498&rfr_iscdi=true |