{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:20:51Z","timestamp":1787016051344,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,2,27]],"date-time":"2017-02-27T00:00:00Z","timestamp":1488153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004825","name":"Nordea-fonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004836","name":"Det Frie Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["11\u2010108354"],"award-info":[{"award-number":["11\u2010108354"]}],"id":[{"id":"10.13039\/501100004836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007398","name":"Strategiske Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["11\u2010115818"],"award-info":[{"award-number":["11\u2010115818"]}],"id":[{"id":"10.13039\/100007398","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["06CVD"],"award-info":[{"award-number":["06CVD"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005865","name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007664","name":"Manpei Suzuki Diabetes Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,6,15]]},"abstract":"<jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Pre\u2010ischaemic administration of aminooxiacetate (AOA), an inhibitor of the malate\u2010aspartate shuttle (MAS), provides cardioprotection against ischaemia\u2013reperfusion injury. The underlying mechanism remains unknown.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We examined whether transient inhibition of the MAS during ischaemia and early reperfusion by AOA treatment could prevent mitochondrial damage at later reperfusion.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The AOA treatment preserved mitochondrial respiratory capacity with reduced mitochondrial oxidative stress during late reperfusion to the same extent as ischaemic preconditioning (IPC).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>However, AOA treatment, but not IPC, reduced the myocardial interstitial concentration of tricarboxylic acid cycle intermediates at the onset of reperfusion.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The results obtained in the present study demonstrate that metabolic regulation by inhibition of the MAS at the onset of reperfusion may be beneficial for the preservation of mitochondrial function during late reperfusion in an IR\u2010injured heart.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Mitochondrial dysfunction plays a central role in ischaemia\u2013reperfusion (IR) injury. Pre\u2010ischaemic administration of aminooxyacetate (AOA), an inhibitor of the malate\u2010aspartate shuttle (MAS), provides cardioprotection against IR injury, although the underlying mechanism remains unknown. We hypothesized that a transient inhibition of the MAS during ischaemia and early reperfusion could preserve mitochondrial function at later phase of reperfusion in the IR\u2010injured heart to the same extent as ischaemic preconditioning (IPC), which is a well\u2010validated cardioprotective strategy against IR injury. In the present study, we show that pre\u2010ischaemic administration of AOA preserved mitochondrial complex I\u2010linked state 3 respiration and fatty acid oxidation during late reperfusion in IR\u2010injured isolated rat hearts. AOA treatment also attenuated the excessive emission of mitochondrial reactive oxygen species during state 3 with complex I\u2010linked substrates during late reperfusion, which was consistent with reduced oxidative damage in the IR\u2010injured heart. As a result, AOA treatment reduced infarct size after reperfusion. These protective effects of MAS inhibition on the mitochondria were similar to those of IPC. Intriguingly, the protection of mitochondrial function by AOA treatment appears to be different from that of IPC because AOA treatment, but not IPC, downregulated myocardial tricarboxilic acid (TCA)\u2010cycle intermediates at the onset of reperfusion. MAS inhibition thus preserved mitochondrial respiratory capacity and decreased mitochondrial oxidative stress during late reperfusion in the IR\u2010injured heart, at least in part, via metabolic regulation of TCA cycle intermediates in the mitochondria at the onset of reperfusion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp273408","type":"journal-article","created":{"date-parts":[[2017,1,17]],"date-time":"2017-01-17T00:22:57Z","timestamp":1484612577000},"page":"3765-3780","source":"Crossref","is-referenced-by-count":46,"title":["Pre\u2010ischaemic mitochondrial substrate constraint by inhibition of malate\u2010aspartate shuttle preserves mitochondrial function after ischaemia\u2013reperfusion"],"prefix":"10.1113","volume":"595","author":[{"given":"Nichlas Riise","family":"Jespersen","sequence":"first","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5470-6648","authenticated-orcid":false,"given":"Takashi","family":"Yokota","sequence":"additional","affiliation":[{"name":"Xlab, Center for Healthy Aging, Department of Biomedical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaj Brejnholt","family":"St\u00f8ttrup","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Bergdahl","sequence":"additional","affiliation":[{"name":"Department of Exercise Science Concordia University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim Bolther","family":"P\u00e6lestik","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas Agerlund","family":"Povlsen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9970-9535","authenticated-orcid":false,"given":"Flemming","family":"Dela","sequence":"additional","affiliation":[{"name":"Xlab, Center for Healthy Aging, Department of Biomedical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Geriatrics Bispebjerg University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Erik","family":"B\u00f8tker","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1998.0722"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.02.026"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.110262"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3212"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13909"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00727.2014"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.01.016"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7827(01)00024-8"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705891104"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.03.005"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"7809","DOI":"10.1016\/S0021-9258(18)53030-1","article-title":"Inhibition of glycolysis by amino acids in ascites tumor cells. 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