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Outstanding Young Talent Training Plan","award":["20192ACB21030"],"award-info":[{"award-number":["20192ACB21030"]}]},{"name":"Innovation of Science and Technology in Jiangxi Province Outstanding Young Talent Training Plan","award":["20192ACBL20036"],"award-info":[{"award-number":["20192ACBL20036"]}]},{"name":"Innovation of Science and Technology in Jiangxi Province Outstanding Young Talent Training Plan","award":["20181BAB205003"],"award-info":[{"award-number":["20181BAB205003"]}]},{"name":"Innovation of Science and Technology in Jiangxi Province Outstanding Young Talent Training Plan","award":["20192BCBL23022"],"award-info":[{"award-number":["20192BCBL23022"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Myocardial ischemia\/reperfusion injury is associated with adverse cardiovascular outcomes after acute myocardial infarction. However, the molecular mechanism of ischemia\/reperfusion injury remains unclear. Mitochondria dysfunction is a participant in and regulator of myocardial ischemia-reperfusion injury. However, the molecular mechanisms involved in this process are not yet fully understood. We previously reported that Notch1 can reduce mitochondrial lysis, reduce myocardial infarct size, and inhibit ventricular remodeling. Herein, we explore the role of the downstream target Notch1 in mitochondrial regulation. Methods: This study constructs an ischemic\/reperfusion injury rat model and a hypoxia\/reoxygenation cell model. The expression of PTEN is detected by real-time PCR, Western blot, and immunofluorescence staining. Cell viability is analyzed with CCK-8. Apoptosis level is detected via the TUNEL assay, and mitochondrial fission\/fusion is analyzed with MitoTracker Green staining. Cardiac troponin I (cTnI), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and CK levels of creatine kinase-MB (CK) are measured with ELISA kits. Results: We found that PETN-Pink1-Parkin signaling is inhibited by Notch1 I\/R in injured neonatal cardiomyocytes and hearts, i.e., via the inhibition of mitochondrial dysfunction and fragmentation. With the recure of PTEN or Pink1, the protective effect of Notch1 was largely diminished. Conclusion: These results suggest that N1ICD acts protectively against ischemic reperfusion injury by suppressing PTEN-Pink1-mediated mitochondrial dysfunction and fragmentation.<\/jats:p>","DOI":"10.3390\/cells12010137","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T03:14:28Z","timestamp":1672370068000},"page":"137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Notch1 Protects against Ischemic-Reperfusion Injury by Suppressing PTEN-Pink1-Mediated Mitochondrial Dysfunction and Mitophagy"],"prefix":"10.3390","volume":"12","author":[{"given":"Qirong","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, The First Affiliated Hospital, Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Jiangxi Hospital of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qicai","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2879-2882","authenticated-orcid":false,"given":"Xueliang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41569-020-0403-y","article-title":"Myocardial ischaemia-reperfusion injury and cardioprotection in perspective","volume":"17","author":"Heusch","year":"2020","journal-title":"Nat. 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