Melatonin attenuates myocardial ischemia‐reperfusion injury via improving mitochondrial fusion/mitophagy and activating the AMPK‐OPA1 signaling pathways

Journal of Pineal Research, Journal Year: 2018, Volume and Issue: 66(2)

Published: Dec. 5, 2018

Abstract Optic atrophy 1 (OPA1)‐related mitochondrial fusion and mitophagy are vital to sustain homeostasis under stress conditions. However, no study has confirmed whether OPA1‐related fusion/mitophagy is activated by melatonin and, consequently, attenuates cardiomyocyte death in the setting of cardiac ischemia‐reperfusion (I/R) injury. Our results indicated that OPA1, fusion, were significantly repressed I/R injury, accompanied infarction area expansion, heart dysfunction, myocardial inflammation, oxidative stress. treatment maintained function viability, these effects highly dependent on fusion/mitophagy. At molecular level, fusion/mitophagy, which was normalized melatonin, substantially rectified excessive fission, promoted mitochondria energy metabolism, sustained function, blocked caspase‐9‐involved apoptosis. genetic approaches with a cardiac‐specific knockout OPA1 abolished beneficial survival vivo vitro. Furthermore, we demonstrated affected stabilization via AMPK signaling pathway blockade expression compromised cardioprotective action melatonin. Overall, our confirm actually modulated Moreover, manipulation AMPK‐OPA1‐mitochondrial axis may be novel therapeutic approach reduce

Language: Английский

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New insights into the role of mitochondria in cardiac microvascular ischemia/reperfusion injury

Angiogenesis, Journal Year: 2020, Volume and Issue: 23(3), P. 299 - 314

Published: April 3, 2020

Language: Английский

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Role of mitochondrial quality surveillance in myocardial infarction: From bench to bedside

Ageing Research Reviews, Journal Year: 2020, Volume and Issue: 66, P. 101250 - 101250

Published: Dec. 31, 2020

Language: Английский

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Empagliflozin attenuates cardiac microvascular ischemia/reperfusion through activating the AMPKα1/ULK1/FUNDC1/mitophagy pathway

Redox Biology, Journal Year: 2022, Volume and Issue: 52, P. 102288 - 102288

Published: March 18, 2022

Mitophagy preserves microvascular structure and function during myocardial ischemia/reperfusion (I/R) injury. Empagliflozin, an anti-diabetes drug, may also protect mitochondria. We explored whether empagliflozin could reduce cardiac I/R injury by enhancing mitophagy. In mice, induced luminal stenosis, microvessel wall damage, erythrocyte accumulation perfusion defects in the microcirculation. Additionally, triggered endothelial hyperpermeability neutrophil infiltration, which upregulated adhesive factors endothelin-1 but downregulated vascular cadherin nitric oxide synthase heart tissue. vitro, impaired barrier integrity of cells (CMECs), while preserved CMEC homeostasis thus maintained function. activated mitochondrial fission, oxidative stress apoptotic signaling CMECs, whereas normalized fission fusion, neutralized supraphysiologic reactive oxygen species concentrations suppressed apoptosis. Empagliflozin exerted these protective effects activating FUNDC1-dependent mitophagy through AMPKα1/ULK1 pathway. Both vitro vivo, genetic ablation AMPKα1 or FUNDC1 abolished beneficial on microvasculature CMECs. Taken together, preservation activation AMPKα1/ULK1/FUNDC1/mitophagy pathway is working mechanism attenuating

Language: Английский

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Mitochondrial quality control mechanisms as therapeutic targets in doxorubicin-induced cardiotoxicity

Trends in Pharmacological Sciences, Journal Year: 2022, Volume and Issue: 44(1), P. 34 - 49

Published: Nov. 14, 2022

Language: Английский

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Molecular Mechanisms of Mitochondrial Quality Control in Ischemic Cardiomyopathy

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 19(2), P. 426 - 448

Published: Dec. 19, 2022

Ischemic cardiomyopathy (ICM) is a special type of coronary heart disease or an advanced stage the disease, which related to pathological mechanism primary dilated cardiomyopathy. mainly occurs in long-term myocardial ischemia, resulting diffuse fibrosis. This turn affects cardiac ejection function, significant impact on systolic and diastolic decrease fraction. The pathogenesis ICM closely disease. Mainly due atherosclerosis caused by stenosis vascular occlusion, causing inflammatory lesions thrombosis. As progresses, it leads ischemia eventually ICM. mechanisms inflammation, hypertrophy, fibrosis remodeling. Mitochondria are organelles with double-membrane structure, so composition mitochondrial outer compartment basically similar that cytoplasm. When ischemia-reperfusion induces large influx calcium into cell, concentration ions also increases. subsequent opening membrane permeability transition pore inner overload homeostasis cardiomyocytes activates pathway apoptosis. Mitochondrial Quality Control (MQC), as important for regulating function cardiomyocytes, morphological structure/function lifespan mitochondria. In this review, we discuss role MQC (including mitophagy, dynamics, biosynthesis) provide evidence targeting

Language: Английский

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TMBIM6 prevents VDAC1 multimerization and improves mitochondrial quality control to reduce sepsis-related myocardial injury

Metabolism, Journal Year: 2023, Volume and Issue: 140, P. 155383 - 155383

Published: Jan. 2, 2023

Language: Английский

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Vitamin C as Scavenger of Reactive Oxygen Species during Healing after Myocardial Infarction

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3114 - 3114

Published: March 7, 2024

Currently, coronary artery bypass and reperfusion therapies are considered the gold standard in long-term treatments to restore heart function after acute myocardial infarction. As a drawback of these restoring strategies, an ischemic insult sudden oxygen exposure lead exacerbated synthesis additional reactive oxidative species persistence increased oxidation levels. Attempts based on antioxidant treatment have failed achieve effective therapy for cardiovascular disease patients. The controversial use vitamin C as clinical practice is comprehensively systematized discussed this review. dose-dependent adsorption release kinetics mechanism complex; however, review may provide holistic perspective its potential preventive supplement and/or combined precise targeted therapeutics management therapy.

Language: Английский

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Bax inhibitor 1 preserves mitochondrial homeostasis in acute kidney injury through promoting mitochondrial retention of PHB2

Theranostics, Journal Year: 2019, Volume and Issue: 10(1), P. 384 - 397

Published: Nov. 7, 2019

Bax inhibitor-1 (BI1) conveys anti-apoptotic signals for mitochondria while prohibitin 2 (PHB2) is implicated in sustaining mitochondrial morphology and function. However, their regulatory roles acute kidney injury (AKI) are largely unknown. Methods: In human patients with AKI, levels of BI1 urine plasma were determined using ELISA. An experimental model AKI was established ATP depletion-mediated metabolic stress ischemia-reperfusion (IRI) primary tubule cells transgenic mice, respectively. Western blots, ELISA, qPCR, immunofluorescence, RNA silencing, domain deletion assay employed to evaluate the PHB2 preservation integrity. Results: Levels decreased its expression correlated inversely renal reconstitution a murine capable alleviating failure, inflammation tubular death. Further molecular scrutiny revealed that preserved genetic integrity, reduced oxidative stress, promoted respiration, inhibited excessive fission, improved mitophagy suppressed apoptosis. Intriguingly, mitochondria-localized sustained by knockdown abolished mitochondrial- renal- protective properties BI1. Furthermore, retention within through direct interaction cytoplasmic facilitate import. This confirmed observation C-terminus PHB required BI1-PHB2 cross-linking. Conclusion: Our data have unveiled an essential role as master regulator function localization PHB2, revealing novel therapeutic promises against AKI.

Language: Английский

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SERCA Overexpression Improves Mitochondrial Quality Control and Attenuates Cardiac Microvascular Ischemia-Reperfusion Injury

Molecular Therapy — Nucleic Acids, Journal Year: 2020, Volume and Issue: 22, P. 696 - 707

Published: Sept. 16, 2020

Despite significant advances in the treatment of myocardial ischemia-reperfusion (I/R) injury, coronary circulation is a so far neglected target cardioprotection. In this study, we investigated molecular mechanisms underlying I/R injury to cardiac microcirculation. Using gene delivery, analyzed microvascular protective effects sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) on reperfused heart and examined role SERCA regulating mitochondrial quality control endothelial cells (CMECs). Our data showed that overexpression attenuates lumen stenosis, inhibits microthrombus formation, reduces inflammation response, improves endothelium-dependent vascular relaxation. vitro experiments demonstrated viability, barrier integrity, cytoskeleton assembly CMECs. Mitochondrial control, including fusion, mitophagy, bioenergetics, biogenesis, were disrupted by but restored overexpression. also inhibiting calcium overload, inactivating xanthine oxidase (XO), reducing intracellular/mitochondrial reactive oxygen species (ROS). Administration exogenous XO or channel agonist abolished offset beneficial after injury. These findings indicate may be an effective approach targeting calcium/XO/ROS signaling preserving control.

Language: Английский

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