Article ; Online: The additive effects of nicotinamide mononucleotide and melatonin on mitochondrial biogenesis and fission/fusion, autophagy, and microRNA-499 in the aged rat heart with reperfusion injury.
Naunyn-Schmiedeberg's archives of pharmacology
2023 Volume 396, Issue 8, Page(s) 1701–1711
Abstract: The prognosis of myocardial ischemia/reperfusion (I/R) injury is poor in elderly patients. Aging increases the susceptibility of the heart to cell death from I/R injury and prevents the optimal effectiveness of cardioprotective modalities. Since the ... ...
| Abstract | The prognosis of myocardial ischemia/reperfusion (I/R) injury is poor in elderly patients. Aging increases the susceptibility of the heart to cell death from I/R injury and prevents the optimal effectiveness of cardioprotective modalities. Since the interaction of aging with cardioprotection is multifactorial, combination therapy may overcome the above-mentioned burden through correcting various components of the injury. Here, we explored the effects of nicotinamide mononucleotide (NMN)/melatonin combination therapy on mitochondrial biogenesis and fission/fusion, autophagy, and microRNA-499 in the aged rat heart with reperfusion injury. Ex vivo model of myocardial I/R injury was established by coronary occlusion and re-opening in 30 aged male Wistar rats (400-450 g, 22-24 months old). NMN (100 mg/kg/48 h, intraperitoneally) was administered over 28 days before I/R, and melatonin (50 µM) was added to the perfusion solution at early reperfusion. CK-MB release and expression of mitochondrial biogenesis genes and proteins, mitochondrial fission/fusion proteins, autophagy genes, and microRNA-499 were assessed. NMN/melatonin combination therapy concomitantly decreased CK-MB release in aged reperfused hearts (P < .001). It also upregulated SIRT1/PGC-1α/Nrf1/TFAM profiles at both gene and protein levels, Mfn2 protein, and microRNA-499 expression, and downregulated Drp1 protein and Beclin1, LC3, and p62 genes (P < .05 to P < .001). The effect of combination therapy was greater than individual ones. Co-application of NMN/melatonin within the setting of I/R injury in the aged rat heart induced noticeable cardioprotection through modulation of a coordinated network including microRNA-499 expression along with mitochondrial biogenesis associated with SIRT1/PGC-1α/Nrf1/TFAM profiles, mitochondrial fission/fusion, and autophagy, therefore, appears to prevent the burden of myocardial I/R injury in elderly patients. |
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| MeSH term(s) | Rats ; Animals ; Male ; Melatonin/pharmacology ; Melatonin/therapeutic use ; Nicotinamide Mononucleotide/pharmacology ; Nicotinamide Mononucleotide/therapeutic use ; Sirtuin 1/genetics ; Sirtuin 1/metabolism ; Organelle Biogenesis ; Rats, Wistar ; Reperfusion Injury ; Myocardial Reperfusion Injury/drug therapy ; Myocardial Reperfusion Injury/genetics ; Myocardial Reperfusion Injury/prevention & control ; Autophagy ; MicroRNAs/genetics |
| Chemical Substances | Melatonin (JL5DK93RCL) ; Nicotinamide Mononucleotide (1094-61-7) ; Sirtuin 1 (EC 3.5.1.-) ; MicroRNAs ; MIRN499 microRNA, rat |
| Language | English |
| Publishing date | 2023-02-18 |
| Publishing country | Germany |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 121471-8 |
| ISSN | 1432-1912 ; 0028-1298 |
| ISSN (online) | 1432-1912 |
| ISSN | 0028-1298 |
| DOI | 10.1007/s00210-023-02383-y |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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