{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T16:38:28Z","timestamp":1785602308131,"version":"3.56.0"},"reference-count":69,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2020,9,15]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Ischemic heart disease is the leading cause of morbidity and mortality worldwide. Ischemic preconditioning (IPC) is the most powerful intrinsic protection against cardiac ischemia\/reperfusion injury. Previous studies have shown that a multifunctional TRIM family protein, MG53 (mitsugumin 53; also called TRIM72), not only plays an essential role in IPC-mediated cardioprotection against ischemia\/reperfusion injury but also ameliorates mechanical damage. In addition to its intracellular actions, as a myokine\/cardiokine, MG53 can be secreted from the heart and skeletal muscle in response to metabolic stress. However, it is unknown whether IPC-mediated cardioprotection is causally related to MG53 secretion and, if so, what the underlying mechanism is.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Using proteomic analysis in conjunction with genetic and pharmacological approaches, we examined MG53 secretion in response to IPC and explored the underlying mechanism using rodents in in vivo, isolated perfused hearts, and cultured neonatal rat ventricular cardiomyocytes. Moreover, using recombinant MG53 proteins, we investigated the potential biological function of secreted MG53 in the context of IPC and ischemia\/reperfusion injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              We found that IPC triggered robust MG53 secretion in rodents in vivo, perfused hearts, and cultured cardiac myocytes without causing cell membrane leakage. Mechanistically, IPC promoted MG53 secretion through H\n              <jats:sub>2<\/jats:sub>\n              O\n              <jats:sub>2<\/jats:sub>\n              -evoked activation of protein kinase-C-\u03b4. Specifically, IPC-induced myocardial MG53 secretion was mediated by H\n              <jats:sub>2<\/jats:sub>\n              O\n              <jats:sub>2<\/jats:sub>\n              -triggered phosphorylation of protein kinase-C-\u03b4 at Y311, which is necessary and sufficient to facilitate MG53 secretion. Functionally, systemic delivery of recombinant MG53 proteins to mimic elevated circulating MG53 not only restored IPC function in MG53-deficient mice but also protected rodent hearts from ischemia\/reperfusion injury even in the absence of IPC. Moreover, oxidative stress by H\n              <jats:sub>2<\/jats:sub>\n              O\n              <jats:sub>2<\/jats:sub>\n              augmented MG53 secretion, and MG53 knockdown exacerbated H\n              <jats:sub>2<\/jats:sub>\n              O\n              <jats:sub>2<\/jats:sub>\n              -induced cell injury in human embryonic stem cell\u2013derived cardiomyocytes, despite relatively low basal expression of MG53 in human heart.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              We conclude that IPC and oxidative stress can trigger MG53 secretion from the heart via an H\n              <jats:sub>2<\/jats:sub>\n              O\n              <jats:sub>2<\/jats:sub>\n              \u2013protein kinase-C-\u03b4\u2013dependent mechanism and that extracellular MG53 can participate in IPC protection against cardiac ischemia\/reperfusion injury.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.119.044998","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T09:00:16Z","timestamp":1594976416000},"page":"1077-1091","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":48,"title":["Cardiac Ischemic Preconditioning Promotes MG53 Secretion Through H\n            <sub>2<\/sub>\n            O\n            <sub>2<\/sub>\n            -Activated Protein Kinase C-\u03b4 Signaling"],"prefix":"10.1161","volume":"142","author":[{"given":"Dan","family":"Shan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine (D.S., S.G., H.-K.W., F. Lv, L.J., M.Z., P.X., Y.W., Y.S., X.H., C.-M.C., Y.Z., R.-P.X.), Peking University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8070-2760","authenticated-orcid":true,"given":"Sile","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine (D.S., S.G., H.-K.W., F. Lv, L.J., M.Z., P.X., Y.W., Y.S., X.H., C.-M.C., Y.Z., R.-P.X.), Peking University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Kun","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine (D.S., S.G., H.-K.W., F. Lv, L.J., M.Z., P.X., Y.W., Y.S., X.H., C.-M.C., Y.Z., R.-P.X.), Peking University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxiang","family":"Lv","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine (D.S., S.G., H.-K.W., F. Lv, L.J., M.Z., P.X., Y.W., Y.S., X.H., C.-M.C., Y.Z., R.-P.X.), Peking University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine (D.S., S.G., H.-K.W., F. Lv, L.J., M.Z., P.X., Y.W., Y.S., X.H., C.-M.C., Y.Z., R.-P.X.), Peking University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5283-6497","authenticated-orcid":true,"given":"Mao","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine (D.S., S.G., H.-K.W., F. Lv, L.J., M.Z., P.X., Y.W., Y.S., X.H., C.-M.C., Y.Z., R.-P.X.), Peking University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine (D.S., S.G., H.-K.W., F. 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Lv, L.J., M.Z., P.X., Y.W., Y.S., X.H., C.-M.C., Y.Z., R.-P.X.), Peking University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fujian","family":"Wu","sequence":"additional","affiliation":[{"name":"Beijing Laboratory for Cardiovascular Precision Medicine, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Collaborative Innovation Center for Cardiovascular Disorders, Anzhen Hospital, Capital Medical University, China (F.W., F. Lan)."},{"name":"Beijing Institute of Heart, Lung and Blood Vessel Diseases, China (F.W., F. Lan)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Lan","sequence":"additional","affiliation":[{"name":"Beijing Laboratory for Cardiovascular Precision Medicine, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Collaborative Innovation Center for Cardiovascular Disorders, Anzhen Hospital, Capital Medical University, China (F.W., F. Lan)."},{"name":"Beijing Institute of Heart, Lung and Blood Vessel Diseases, China (F.W., F. Lan)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinli","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine (D.S., S.G., H.-K.W., F. 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