Exogenous spermine inhibits hypoxia/ischemia-induced myocardial apoptosis via regulation of mitochondrial permeability transition pore and associated pathways
Open accessAbstract
Myocardial infarction (MI) is associated with a high mortality rate, which is attributed to the effects of myocyte loss that occurs as a result of ischemia-induced cell death. Very few therapies can effectively prevent or delay the effects of ischemia. Polyamines (PAs) are polycations required for cell growth and division, and their use may prevent cell loss. The aim of this study was to investigate the relationship between hypoxia/ischemia (H/I)-induced cell apoptosis and PA metabolism and to investigate the ability of spermine to limit H/I injury in cardiomyocytes by blocking the mitochondrial apoptotic pathway. Neonatal rat cardiomyocytes were placed under hypoxic conditions for 24 h after being subjected to 5 μM of spermine as a pretreatment therapy. H/I induced PA catabolism, which was indicated by a 1.3-fold up-regulation of spermidine/spermine N(1)-acetyltransferase expression. Exogenous spermine significantly reduced H/I-induced cell death rate (60 ± 2 to 36 ± 2%) and apoptosis rate (42 ± 2 to 21 ± 2%); it also attenuated lactate dehyodrogenase and creatine kinase leakage (440 ± 13 and 336 ± 16 U/L to 275 ± 15 and 235 ± 13 U/L). Furthermore, it decreases calcium overload (3.8 ± 0.2 to 2.2 ± 0.1 a.u.). Moreover, spermine pretreatment remarkably decreased cytochrome c release from the mitochondria to the cytosol, lowering the expression of cleaved caspase-3 and -9. With spermine pretreatment, there was an increase in Bcl-2 levels and phosphorylation of ERK1/2, phosphoinositide 3-kinase, Akt, and GSK-3β, preserving mitochondrial membrane potential and inducing an mitochondrial permeability transition pore opening. In conclusion, H/I decreased endogenous spermine concentrations in cardiomyocytes, which ultimately induced apoptosis. The addition of exogenous spermine effectively prevented myocyte cell death.
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Spermine, a metabolite of spermidine, has a cardioprotection effect.
“Spermine, a metabolite of spermidine, also has a cardioprotection effect [279].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [279]
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- Authors
- Wei, C., Li, H., Wang, Y., Peng, X., Shao, H., Li, H., Bai, S., & Xu, C.
- Affiliations
- Harbin Medical University (CN)
- Department of Pathophysiology, Harbin Medical University, Harbin 150081, China
- Corresponding author
- Xu, Changqing
- Venue
- Experimental Biology and Medicine
- Publisher
- Frontiers Media SA
- Published
- 2016-07-24
- Volume
- 241
- Issue
- 14
- Pages
- 1505-1515
- ISSN
- 0071-3384 (ISSN-L)
- 1535-3702
- 1535-3699
- PMC
- PMC4994901
- OpenAlex
- W2345177562
- Cited by
- 32
- References
- 34
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 7 · 2018: 3 · 2017: 5 · 2014: 1
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Biology and Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81270311, 81070123)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- spermine, polyamines, myocardial ischemia-reperfusion injury, cardiomyocyte apoptosis, mitochondrial permeability transition pore, cytochrome c release, caspase-3, caspase-9, Bcl-2, ERK signaling, calcium overload, mitochondrial membrane potential, cardioprotection, neonatal rat cardiomyocytes
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Animals, Permeability, Phosphorylation, Spermine, Cell Hypoxia, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Phosphatidylinositol 3-Kinases, Mitogen-Activated Protein Kinase 1, Myocytes, Cardiac, Mitogen-Activated Protein Kinase 3, Proto-Oncogene Proteins c-akt, Mitochondrial Membranes, Rats, Membrane Potential, Mitochondrial
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