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Notch1 Protects against Ischemic-Reperfusion Injury by Suppressing PTEN-Pink1-Mediated Mitochondrial Dysfunction and Mitophagy

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-...

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Autores principales: Xu, Qirong, Liu, Sheng, Gong, Qiang, Zhu, Rongrong, Liu, Jichun, Wu, Qicai, Zhou, Xueliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818205/
https://www.ncbi.nlm.nih.gov/pubmed/36611931
http://dx.doi.org/10.3390/cells12010137
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author Xu, Qirong
Liu, Sheng
Gong, Qiang
Zhu, Rongrong
Liu, Jichun
Wu, Qicai
Zhou, Xueliang
author_facet Xu, Qirong
Liu, Sheng
Gong, Qiang
Zhu, Rongrong
Liu, Jichun
Wu, Qicai
Zhou, Xueliang
author_sort Xu, Qirong
collection PubMed
description 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.
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spelling pubmed-98182052023-01-07 Notch1 Protects against Ischemic-Reperfusion Injury by Suppressing PTEN-Pink1-Mediated Mitochondrial Dysfunction and Mitophagy Xu, Qirong Liu, Sheng Gong, Qiang Zhu, Rongrong Liu, Jichun Wu, Qicai Zhou, Xueliang Cells Article 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. MDPI 2022-12-29 /pmc/articles/PMC9818205/ /pubmed/36611931 http://dx.doi.org/10.3390/cells12010137 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xu, Qirong
Liu, Sheng
Gong, Qiang
Zhu, Rongrong
Liu, Jichun
Wu, Qicai
Zhou, Xueliang
Notch1 Protects against Ischemic-Reperfusion Injury by Suppressing PTEN-Pink1-Mediated Mitochondrial Dysfunction and Mitophagy
title Notch1 Protects against Ischemic-Reperfusion Injury by Suppressing PTEN-Pink1-Mediated Mitochondrial Dysfunction and Mitophagy
title_full Notch1 Protects against Ischemic-Reperfusion Injury by Suppressing PTEN-Pink1-Mediated Mitochondrial Dysfunction and Mitophagy
title_fullStr Notch1 Protects against Ischemic-Reperfusion Injury by Suppressing PTEN-Pink1-Mediated Mitochondrial Dysfunction and Mitophagy
title_full_unstemmed Notch1 Protects against Ischemic-Reperfusion Injury by Suppressing PTEN-Pink1-Mediated Mitochondrial Dysfunction and Mitophagy
title_short Notch1 Protects against Ischemic-Reperfusion Injury by Suppressing PTEN-Pink1-Mediated Mitochondrial Dysfunction and Mitophagy
title_sort notch1 protects against ischemic-reperfusion injury by suppressing pten-pink1-mediated mitochondrial dysfunction and mitophagy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818205/
https://www.ncbi.nlm.nih.gov/pubmed/36611931
http://dx.doi.org/10.3390/cells12010137
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