{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:49:43Z","timestamp":1789145383849,"version":"build-2803163510"},"reference-count":65,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2017,10,22]],"date-time":"2017-10-22T00:00:00Z","timestamp":1508630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006772","name":"Max and Minnie Tomerlin Voelcker Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006772","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL138093"],"award-info":[{"award-number":["HL138093"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["17SDG33100000"],"award-info":[{"award-number":["17SDG33100000"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Recent evidence indicates that GPER (G protein\u2010coupled oestrogen receptor 1) mediates acute pre\u2010ischaemic oestrogen\u2010induced protection of the myocardium from ischaemia\/reperfusion injury\n                      <jats:italic>via<\/jats:italic>\n                      a signalling cascade that includes PKC translocation, ERK1\/2\/ GSK\u20103\u03b2 phosphorylation and inhibition of the mitochondrial permeability transition pore (mPTP) opening. Here, we investigated the impact and mechanism involved in post\u2010ischaemic GPER activation in ischaemia\/reperfusion injury. We determined whether GPER activation at the onset of reperfusion confers cardioprotective effects by protecting against mitochondrial impairment and mitophagy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vivo<\/jats:italic>\n                      rat hearts were subjected to ischaemia followed by reperfusion with oestrogen (17\u03b2\u2010oestradiol, E2), E2\u00a0+\u00a0G15, a GPER antagonist, or vehicle. Myocardial infarct size, the threshold for the opening of mPTP, mitophagy, mitochondrial membrane potential, ROS production, proteins ubiquitinated including cyclophilin D, and phosphorylation levels of ERK and GSK\u20103\u03b2 were measured.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that post\u2010ischaemic E2 administration to both male and female ovariectomized\u2010rats reduced myocardial infarct size. Post\u2010ischaemic E2 administration preserved mitochondrial structural integrity and this was associated with a decrease in ROS production and increased mitochondrial membrane potential, as well as an increase in the mitochondrial Ca\n                      <jats:sup>2+<\/jats:sup>\n                      load required to induce mPTP opening\n                      <jats:italic>via<\/jats:italic>\n                      activation of the MEK\/ERK\/GSK\u20103\u03b2 axis. Moreover, E2 reduced mitophagy\n                      <jats:italic>via<\/jats:italic>\n                      the PINK1\/Parkin pathway involving LC3I, LC3II and p62 proteins. All these post\u2010ischaemic effects of E2 were abolished by G15 suggesting a GPER\u2010dependent mechanism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results indicate that post\u2010ischaemic GPER activation induces cardioprotective effects against ischaemia\/reperfusion injury in males and females by protecting mitochondrial structural integrity and function and reducing mitophagy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.14033","type":"journal-article","created":{"date-parts":[[2017,9,14]],"date-time":"2017-09-14T11:35:18Z","timestamp":1505388918000},"page":"4329-4344","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":118,"title":["Activation of G protein\u2010coupled oestrogen receptor 1 at the onset of reperfusion protects the myocardium against ischemia\/reperfusion injury by reducing mitochondrial dysfunction and mitophagy"],"prefix":"10.1111","volume":"174","author":[{"given":"Yansheng","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Cellular and Integrative Physiology, School of Medicine University of Texas Health Science Center at San Antonio  San Antonio TX USA"},{"name":"Department of Pathophysiology Xinxiang Medical University  Xinxiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngonidzashe B","family":"Madungwe","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, School of Medicine University of Texas Health Science Center at San Antonio  San Antonio TX USA"},{"name":"Department of Biomedical Engineering University of Texas at San Antonio  San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina Victoria","family":"da Cruz Junho","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, School of Medicine University of Texas Health Science Center at San Antonio  San Antonio TX USA"},{"name":"Center of Natural and Human Sciences Federal University of ABC  Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3667-5790","authenticated-orcid":false,"given":"Jean C","family":"Bopassa","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, School of Medicine University of Texas Health Science Center at San Antonio  San Antonio TX 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