Alkbh5 promotes Ythdf1 expression through demethylation thereby facilitating Fth1 translation to inhibit ferroptosis of myocardial infarction DOI Creative Commons
Min Yin,

Heping Liu

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

Alkbh5 promotes Ythdf1 expression through demethylation thereby facilitating Fth1 translation to inhibit ferroptosis of myocardial infarction DOI Creative Commons
Min Yin,

Heping Liu

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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