Abstract
Myocardial ischemia/reperfusion (I/R) injury can stimulate mitochondrial reactive oxygen species production. Optic atrophy 1- (OPA1-) induced mitochondrial fusion is an endogenous antioxidative mechanism that preserves the mitochondrial function. In our study, we investigated whether melatonin augments OPA1-dependent mitochondrial fusion and thus maintains redox balance during myocardial I/R injury. In hypoxia/reoxygenation- (H/R-) treated H9C2 cardiomyocytes, melatonin treatment upregulated OPA1 mRNA and protein expression, thereby enhancing mitochondrial fusion. Melatonin also suppressed apoptosis in H/R-treated cardiomyocytes, as evidenced by increased cell viability, diminished caspase-3 activity, and reduced Troponin T secretion; however, silencing OPA1 abolished these effects. H/R treatment augmented mitochondrial ROS production and repressed antioxidative molecule levels, while melatonin reversed these changes in an OPA1-dependent manner. Melatonin also inhibited mitochondrial permeability transition pore opening and maintained the mitochondrial membrane potential, but OPA1 silencing prevented these outcomes. These results illustrate that melatonin administration alleviates cardiomyocyte I/R injury by activating OPA1-induced mitochondrial fusion and inhibiting mitochondrial oxidative stress.
Highlights
Myocardial reperfusion with thrombolysis can effectively save the viable heart muscle and limit the myocardial infarction area [1]
There are four major manifestations of myocardial I/R injury: (1) reperfusion-induced ventricular arrhythmia; (2) myocardial stunning, a type of systolic dysfunction that occurs when oxidative stress and endoplasmic reticulum calcium imbalance impairs cardiomyocyte contractile elements; (3) microvascular obstruction, the inability to reperfuse the ischemic site due to capillary injury, impaired vasodilation, external capillary compression caused by myocardial swelling, microembolism caused by arteriosclerotic plaque fragments, platelet microthrombosis, soluble vasomotor, thrombogenic substance release, and neutrophil blockage; and (4) fatal myocardial reperfusion injury, the death of viable cardiomyocytes due to redox imbalance, abnormal calcium signal, and mitochondrial malfunction [2,3,4,5,6,7]
We performed immunofluorescence analyses, which indicated that the optic atrophy 1 (OPA1) protein expression was rapidly reduced in cardiomyocytes following H/R injury (Figures 1(b) and 1(c))
Summary
Myocardial reperfusion with thrombolysis can effectively save the viable heart muscle and limit the myocardial infarction area [1]. Myocardial ischemia/reperfusion (I/R) injury and cell death often occur in the process of reperfusion; this concept has only recently become widely accepted. The first two manifestations of myocardial I/R injury are reversible, while the latter two are irreversible and lack effective therapeutic approaches. Mitochondria may be damaged during myocardial I/R injury, and mitochondrial damage has been identified as a primary cause of reactive oxygen species (ROS) overproduction [8,9,10]. Mitochondrial fusion has been reported to be reduced during myocardial I/R injury; many clinical protective tools have been created to enhance mitochondrial fusion and inhibit mitochondrial ROS overload [14,15,16]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
