Purpose: Targeting mitochondrial ferroptosis presents a promising strategy for mitigating myocardial ischemia-reperfusion (I/R) injury. This study aims to evaluate the efficacy of the mitochondrial-targeted ferroptosis inhibitor SS-31@Fer-1 (elamipretide@ferrostatin1) in reducing myocardial I/R injury.
Methods: SS-31@Fer-1 was synthesized and applied to H9C2 cells subjected to hypoxia/reoxygenation (H/R) to assess its protective effects. Cytotoxicity was evaluated using a cell counting kit-8 (CCK-8) assay, with lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) levels measured. Mitochondrial reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were assessed using Mito-SOX and JC-1 fluorescent dyes, respectively. Lipid peroxidation products, malondialdehyde (MDA) and glutathione (GSH), were quantified. Mitochondrial structure, mt-cytochrome b (mt-Cytb), and mt-ATP synthase membrane subunit 6 (mt-ATP6) were analyzed. Additionally, iron homeostasis and ferroptosis markers were evaluated.
Results: SS-31@Fer-1 significantly improved H/R-induced cardiomyocyte viability and reduced LDH and CK-MB levels. Compared to the Fer-1 group, SS-31@Fer-1 reduced GSH and increased MDA levels, enhancing mitochondrial integrity and function. Notably, it increased mitochondrial ROS and decreased MMP, indicating a mitigation of H/R-induced cardiomyocyte cytotoxicity. Furthermore, SS-31@Fer-1 maintained cellular iron homeostasis, as evidenced by increased expression of FTH, FTMT, FPN, and ABCB8. Elevated levels of GPX4 and Nrf2 were observed, while ACSL4 and PTGS2 levels were reduced in the SS-31@Fer-1 group.
Conclusions: SS-31@Fer-1 effectively suppressed ferroptosis in H/R-induced cardiomyocytes by maintaining cellular iron homeostasis, improving mitochondrial function, and inhibiting oxidative stress. These findings provide novel insights and opportunities for alleviating myocardial I/R injury.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.biopha.2025.117832 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
SS-31@Fer-1 Alleviates ferroptosis in hypoxia/reoxygenation cardiomyocytes via mitochondrial targeting.
Biomed Pharmacother
January 2025
Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China. Electronic address:
Purpose: Targeting mitochondrial ferroptosis presents a promising strategy for mitigating myocardial ischemia-reperfusion (I/R) injury. This study aims to evaluate the efficacy of the mitochondrial-targeted ferroptosis inhibitor SS-31@Fer-1 (elamipretide@ferrostatin1) in reducing myocardial I/R injury.
Methods: SS-31@Fer-1 was synthesized and applied to H9C2 cells subjected to hypoxia/reoxygenation (H/R) to assess its protective effects.
DNA Damage-Induced Ferroptosis: A Boolean Model Regulating p53 and Non-Coding RNAs in Drug Resistance.
Proteomes
January 2025
Instituto de Matemática e Estatística, Departamento de Ciência da Computação, Universidade de São Paulo, Rua do Matão 1010, São Paulo 05508-090, SP, Brazil.
The tumor suppressor p53, in its wild-type form, plays a central role in cellular homeostasis by regulating senescence, apoptosis, and autophagy within the DNA damage response (DDR). Recent findings suggest that wild-type p53 also governs ferroptosis, an iron-dependent cell death process driven by lipid peroxidation. Post-translational modifications of p53 generate proteoforms that significantly enhance its functional diversity in regulating these mechanisms.
View Article and Find Full Text PDFPlacental Hypoxia-Induced Ferroptosis Drives Vascular Damage in Preeclampsia.
Circ Res
January 2025
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada (C.P., S.A., J.W.A., R.L., F.N., J.S., I.C.).
Background: Iron is an essential micronutrient for cell survival and growth; however, excess of this metal drives ferroptosis. Although maternal iron imbalance and placental hypoxia are independent contributors to the pathogenesis of preeclampsia, a hypertensive disorder of pregnancy, the mechanisms by which their interaction impinge on maternal and placental health remain elusive.
Methods: We used placentae from normotensive and preeclampsia pregnancy cohorts, human H9 embryonic stem cells differentiated into cytotrophoblast-like cells, and placenta-specific preeclamptic mice.
Macranthoside B Suppresses the Growth of Adenocarcinoma of Esophagogastric Junction by Regulating Iron Homeostasis and Ferroptosis through NRF2 Inhibition.
Curr Cancer Drug Targets
January 2025
Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310018, China.
Background: Macranthoside B (MB) is a saponin compound extracted from hon-eysuckle that has been reported to exhibit significant medicinal values, particularly anti-tumor activities. This study aimed to evaluate the anticancer efficacy of MB in treating adenocarci-noma of the esophagogastric junction (AEG) and elucidate its underlying mechanisms.
Methods: Three AEG cell lines and normal gastric epithelial cells were used to assess the an-ticancer activity of MB in vitro.
Cadmium-induced iron dysregulation contributes to functional impairment in brain endothelial cells via the ferroptosis pathway.
Toxicol Appl Pharmacol
January 2025
College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University ERICA Campus, Ansan, South Korea. Electronic address:
Cadmium (Cd) is a heavy metal that is a major hazardous environmental contaminant, ubiquitously present in the environment. Cd exposure has been closely associated with an increased prevalence and severity of neurological and cardiovascular diseases (CVD). The blood-brain barrier (BBB) plays a crucial role in protecting the brain from external environmental factors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!