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SF-PreCon markedly reduced MI\/R injury in DM mice, as evidenced by improved cardiac function (increased LVEF and \u00b1Dp\/dt), decreased infarct size, and decreased apoptosis. To determine the relevant role of AMPK, the effect of SF-PreCon was determined in cardiac-specific AMPK\u03b12 dominant negative expressing mice (AMPK-DN). SF-PreCon decreased MI\/R injury in AMPK-DN mice. To explore the molecular mechanisms responsible for SF-PreCon mediated cardioprotection in DM mice, cell survival molecules were screened. Interestingly, in ND mice, SF-PreCon significantly reduced MI\/R-induced activation of p38, a pro-death MAPK, without altering ERK and JNK. In DM and AMPK-DN mice, the inhibitory effect of SF-PreCon upon p38 activation was significantly blunted. However, SF-PreCon significantly increased phosphorylation of ERK1\/2, a pro-survival MAPK in DM and AMPK-DN mice. We demonstrate that SF-PreCon protects the heart via AMPK-dependent inhibition of pro-death MAPK in ND mice. However, SF-PreCon exerts cardioprotective action via AMPK-independent activation of a pro-survival MAPK member in DM mice. SF-PreCon may be beneficial compared to conventional PreCon in diabetes or clinical scenarios in which AMPK signaling is impaired.<\/jats:p>","DOI":"10.1038\/s41598-019-56897-8","type":"journal-article","created":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T06:03:12Z","timestamp":1578463392000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Sevoflurane Pre-conditioning Ameliorates Diabetic Myocardial Ischemia\/Reperfusion Injury Via Differential Regulation of p38 and ERK"],"prefix":"10.1038","volume":"10","author":[{"given":"Dina","family":"Xie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianli","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyuan","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne Bond","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Christopher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhe","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimin","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinliang","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,8]]},"reference":[{"key":"56897_CR1","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.jacbts.2018.01.005","volume":"3","author":"D Wang","year":"2018","unstructured":"Wang, D. et al. 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