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In experimental models, this mechanism involves GSK3<jats:italic>\u03b2<\/jats:italic>inhibition. HSP90 regulates mitochondrial protein import, with GSK3<jats:italic>\u03b2<\/jats:italic>inhibition increasing HSP90 mitochondrial content. Therefore, we determined whether morphine-induced cardioprotection is mediated by HSP90 and if the protective effect is downstream of GSK3<jats:italic>\u03b2<\/jats:italic>inhibition. Male Sprague-Dawley rats, aged 8\u201310 weeks, were subjected to an<jats:italic>in vivo<\/jats:italic>myocardial ischemia-reperfusion injury protocol involving 30 minutes of ischemia followed by 2 hours of reperfusion. Hemodynamics were continually monitored and myocardial infarct size determined. Rats received morphine (0.3\u2009mg\/kg), the GSK3<jats:italic>\u03b2<\/jats:italic>inhibitor, SB216763 (0.6\u2009mg\/kg), or saline, 10 minutes prior to ischemia. Some rats received selective HSP90 inhibitors, radicicol (0.3\u2009mg\/kg), or deoxyspergualin (DSG, 0.6\u2009mg\/kg) alone or 5 minutes prior to morphine or SB216763. Morphine reduced myocardial infarct size when compared to control (42 \u00b1 2% versus 60 \u00b1 1%). This protection was abolished by prior treatment of radicicol or DSG (59 \u00b1 1%, 56 \u00b1 2%). GSK3<jats:italic>\u03b2<\/jats:italic>inhibition also reduced myocardial infarct size (41 \u00b1 2%) with HSP90 inhibition by radicicol or DSG partially inhibiting SB216763-induced infarct size reduction (54 \u00b1 3%, 47 \u00b1 1%, resp.). These data suggest that opioid-induced cardioprotection is mediated by HSP90. Part of this protection afforded by HSP90 is downstream of GSK3<jats:italic>\u03b2<\/jats:italic>, potentially via the HSP-TOM mitochondrial import pathway.<\/jats:p>","DOI":"10.1155\/2015\/129612","type":"journal-article","created":{"date-parts":[[2015,8,27]],"date-time":"2015-08-27T17:30:29Z","timestamp":1440696629000},"page":"1-8","source":"Crossref","is-referenced-by-count":19,"title":["Morphine Reduces Myocardial Infarct Size via Heat Shock Protein 90 in Rodents"],"prefix":"10.1155","volume":"2015","author":[{"given":"Bryce A.","family":"Small","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna K.","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garrett J.","family":"Gross","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric R.","family":"Gross","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcin.2009.10.015"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1213\/01.ane.0000171931.08371.a2"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)01011-1"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2003.10.008"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.78.6.1100"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000122392.33172.09"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.05878.x"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq154"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000230315.56904.de"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m109.023986"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)01250-3"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00033.2012"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0b013e3181b92201"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-007-0651-6"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9775"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1126\/science.1411548"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.314"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m206236200"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.06.035"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.08.136"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00003.2006"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01195.2006"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1053\/j.jvca.2005.07.036"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1053\/j.jvca.2009.09.012"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8090-8-76"}],"container-title":["BioMed Research International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2015\/129612.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2015\/129612.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2015\/129612.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2016,7,27]],"date-time":"2016-07-27T06:32:54Z","timestamp":1469601174000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.hindawi.com\/journals\/bmri\/2015\/129612\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015]]},"references-count":25,"alternative-id":["129612","129612"],"URL":"https:\/\/doi.org\/10.1155\/2015\/129612","relation":{},"ISSN":["2314-6133","2314-6141"],"issn-type":[{"value":"2314-6133","type":"print"},{"value":"2314-6141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015]]}}}