Alkbh5 promotes Ythdf1 expression through demethylation thereby facilitating Fth1 translation to inhibit ferroptosis of myocardial infarction

BMC Cardiovascular Disorders, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 18, 2025

Myocardial infarction (MI) is a leading cause of global mortality. Ferroptosis, an iron-dependent form programmed cell death, has recently emerged as critical player in cardiovascular diseases. N6-methyladenosine (m6A), the most prevalent RNA methylation modification eukaryotic cells, been implicated various pathological processes; however, its regulatory role MI through ferroptosis remains poorly understood. This study aimed to elucidate mechanism by which m6A mediates via ferroptosis. A hypoxia/reoxygenation (H/R) model was established using H9C2 cells simulate myocardial injury. levels were quantified dot blot assay. Ferroptosis evaluated measuring lactate dehydrogenase (LDH) release, Fe2+ levels, glutathione (GSH), lipid reactive oxygen species (ROS), malondialdehyde (MDA), and apoptosis. The underlying molecular mechanisms investigated western blotting, quantitative real-time PCR (qPCR), methylated immunoprecipitation (MeRIP), RIP. Findings further validated ischemia/reperfusion injury (MIRI) rat model. results revealed that significantly elevated H/R model, accompanied reduced expression Alkbh5 mRNA. Moreover, overexpression inhibited increased Mechanistically, decreased Ythdf1 while promoting Fth1 translation enhancing mRNA expression. Knockdown restored counteracting effects overexpression. Furthermore, alleviated MIRI upregulated expression, protein levels. demonstrates ameliorates inhibiting demethylation Fth1. These findings provide novel insights into highlight potential therapeutic targets for treatment.

Language: Английский

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Advances in flavonoid bioactivity in chronic diseases and bioavailability: transporters and enzymes

Journal of Asian Natural Products Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 29

Published: April 25, 2025

Flavonoids, abundant in the human diet, have been extensively studied for their therapeutic bioactivities. Recent research has made significantly advances our understanding of biological activities flavonoids, demonstrating effects various chronic diseases. However, generally low bioavailability flavonoids limits effectiveness. Therefore, it is essential to explore pharmacokinetics paying particular attention roles transporters and metabolizing enzymes. This paper reviews recent studies on bioactivity highlighting importance metabolic enzymes pharmacokinetics.

Language: Английский

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Ferroptosis and protein translation: emerging perspectives in the research of myocardial infraction

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12

Published: May 2, 2025

Myocardial infarction, as the principal type of ischemic heart disease, has currently become focus research on its prevention and treatment strategies. From perspective myocardial infarction pathogenesis, it is urgent to impede progression this disease improve diagnosis techniques. Ferroptosis, a form programmed cell death mechanistically distinct from apoptosis autophagy, implicated throughout pathogenesis infarction. Dysregulation protein translation leads abnormal expression, disruption cellular signaling, dysfunction, thereby disturbing normal function exacerbating progression. Consequently, clarifying mechanism dysregulation in ferroptosis during will enhance understanding In review, latest progress relationship between collected. The mechanisms by which they regulate are explored, current status role different stages introduced. These findings expected provide valuable insights for pathophysiological precise treatment.

Language: Английский

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Verbascoside attenuates myocardial ischemia/reperfusion-induced ferroptosis following heterotopic heart transplantation via modulating GDF15/GPX4/SLC7A11 pathway

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: May 5, 2025

Myocardial cold ischemia/reperfusion (I/R) injury is an inevitable consequence of heart transplantation, significantly affecting survival rates and therapeutic outcomes. Growth Differentiation Factor 15 (GDF15) has been shown to regulate GPX4-mediated ferroptosis, playing a critical role in mitigating I/R injury. Meanwhile, verbascoside (VB), active compound extracted from the herbaceous plant, demonstrated myocardial protective effects. In this study, transplantation was performed using modified non-suture cuff technique, with VB administered at dose 20 mg/kg/day via intraperitoneal injection for 3 days vivo. vitro, cardiomyocytes were pretreated 50 µg/ml 24 h. treatment reduced histopathological injury, decreased markers, inhibited ferroptosis oxidative stress during vitro experiments further that GDF15 alleviates induced by hypoxic reoxygenation upregulating GPX4. Therefore, it concluded preconditioning can effectively reduce after heterotopic possibly through up-regulation GDF15/GPX4/SLC7A11 pathway.

Language: Английский

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Noncoding RNAs regulating ferroptosis in cardiovascular diseases: novel roles and therapeutic strategies

Molecular and Cellular Biochemistry, Journal Year: 2023, Volume and Issue: 479(11), P. 2827 - 2841

Published: Dec. 8, 2023

Abstract The morbidity and mortality rates of cardiovascular diseases (CVDs) are increasing; thus, they impose substantial health economic burdens worldwide, effective interventions needed for immediate resolution this issue. Recent studies have suggested that noncoding RNAs (ncRNAs) play critical roles in the occurrence development CVDs potential therapeutic targets novel biomarkers these diseases. Newly discovered modes cell death, including necroptosis, pyroptosis, apoptosis, autophagy-dependent death ferroptosis, also key CVD progression. However, which differs from other aforementioned forms regulated terms morphology, biochemistry inhereditability, is a unique iron-dependent mode nonapoptotic induced by abnormal iron metabolism excessive accumulation lipid peroxides reactive oxygen species (ROS). Increasing evidence has confirmed ncRNA-mediated ferroptosis involved regulating tissue homeostasis CVD-related pathophysiological conditions, such as cardiac ischemia/reperfusion (I/R) injury, myocardial infarction (MI), atrial fibrillation (AF), cardiomyopathy heart failure (HF). In review, we summarize underlying mechanism discuss effects provide ideas strategies.

Language: Английский

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