ArticleCardiovascular drugs and therapy2021
Spermine Protects Cardiomyocytes from High Glucose-Induced Energy Disturbance by Targeting the CaSR-gp78-Ubiquitin Proteasome System.
Article in Cardiovascular drugs and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Pathogenesis of diabetic cardiomyopathy and emerging therapeutic strategies: a network-based perspective.Frontiers in clinical diabetes and healthcare · 2026Review
- Spermine delivered by ZIF90 nanoparticles alleviates atherosclerosis by targeted inhibition of macrophage ferroptosis in plaque.Journal of nanobiotechnology · 2025Article
- Spermine: A prospective treatment for high glucose-induced myocardial fibrosis in db/db mice.Iranian journal of basic medical sciences · 2025Article
- Calcium Ion Attenuates Transforming Growth Factor β1-Induced Extracellular Matrix Accumulation by Inducing Smad2 Degradation through the Proteasome Pathway.Bulletin of experimental biology and medicine · 2024Article
- Recent advances associated with cardiometabolic remodeling in diabetes-induced heart failure.American journal of physiology. Heart and circulatory physiology · 2024Review
- SIRT5-related lysine demalonylation of GSTP1 contributes to cardiomyocyte pyroptosis suppression in diabetic cardiomyopathy.International journal of biological sciences · 2024Article
- Gp78 deficiency in hepatocytes alleviates hepatic ischemia-reperfusion injury via suppressing ACSL4-mediated ferroptosis.Cell death & disease · 2023Article
- Exogenous Spermidine Alleviates Diabetic Myocardial Fibrosis Via Suppressing Inflammation and Pyroptosis in db/db MiceBalkan medical journal · 2023Article
- Exogenous spermidine alleviates diabetic cardiomyopathy via suppressing reactive oxygen species, endoplasmic reticulum stress, and Pannexin-1-mediated ferroptosis.Biomolecules & biomedicine · 2023Article
- Elevation of spermine remodels immunosuppressive microenvironment through driving the modification of PD-L1 in hepatocellular carcinoma.Cell communication and signaling : CCS · 2022Article
- Calcium-Sensing Receptor (CaSR)-Mediated Intracellular Communication in Cardiovascular Diseases.Cells · 2022Review
- Transcriptomics Coupled to Proteomics Reveals Novel Targets for the Protective Role of Spermine in Diabetic Cardiomyopathy.Oxidative medicine and cellular longevity · 2022Article
- Proteomic and metabolomic analyses reveal the novel targets of spermine for alleviating diabetic cardiomyopathy in type II diabetic mice.Frontiers in cardiovascular medicine · 2022Article
- Mitochondrial quality control in diabetic cardiomyopathy: from molecular mechanisms to therapeutic strategies.International journal of biological sciences · 2022Review
- Involvement of Polyamines From Cardiac Mast Cells in Myocardial Remodeling Induced by Pressure Overload Through Mitochondrial Permeability Transition Pore Opening.Frontiers in cardiovascular medicine · 2022Article
- Regulating Polyamine Metabolism by miRNAs in Diabetic Cardiomyopathy.Current diabetes reports · 2021Review
- Spermine Regulates Immune and Signal Transduction Dysfunction in Diabetic Cardiomyopathy.Frontiers in endocrinology · 2021Article
- SFRP2 Improves Mitochondrial Dynamics and Mitochondrial Biogenesis, Oxidative Stress, and Apoptosis in Diabetic Cardiomyopathy.Oxidative medicine and cellular longevity · 2021Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo determine the mediation of spermine on energy metabolism disorder and diabetic cardiomyopathy (DCM) development as well as the underlying mechanisms.
methodsAn in vitro model of DCM was established by incubating primary cultured neonatal rat cardiomyocytes with high glucose (HG). Spermine content was assessed by RP-HPLC. The protein levels were detected by western blot. Mitochondrial functions were analyzed using the respiratory chain complex assay kit and immunofluorescence staining.
resultsThe endogenous content of spermine was decreased in the HG group, and the protein levels of ornithine decarboxylase, respiratory chain complex (I-V), mitochondrial fusion-related protein (Mfn1, Mfn2), Cx43, N-cadherin, CaSR, and β-catenin (in cytomembrane) were also down-regulated by HG. In contrast, the protein levels of spermine-N1-acetyltransferase, gp78, Fis1, Drp1, and β-catenin were up-regulated by HG. Meanwhile, we observed that HG increased ubiquitination levels of Mfn1, Mfn2, and Cx43, decreased membrane potential (ΔΨm), and the opening of mitochondrial permeability transport pore (mPTP) followed by intracellular ATP leakage. The supplement of spermine or siRNA-mediated knockdown of gp78 significantly alleviated the detrimental effects of HG, while downregulation of CaSR aggravated the development of DCM. We further confirmed that the lower level of spermine by HG activates the gp78-ubiquitin-proteasome pathway via downregulation of CaSR protein level, which in turn damages mitochondrial gap junction intercellular communication and leads to reduced ATP level.
conclusionThe protective role of spermine on energy metabolism disorder is based on higher CaSR protein level and lower gp78 activation, pointing to the possibility that spermine can be a target for the prevention and treatment of DCM.
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