Natural products and ferroptosis: A novel approach for heart failure management

Phytomedicine, Journal Year: 2025, Volume and Issue: 142, P. 156783 - 156783

Published: April 18, 2025

Language: Английский

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DNA‐PKcs‐Driven YAP1 Phosphorylation and Nuclear Translocation: a Key Regulator of Ferroptosis in Hyperglycemia‐Induced Cardiac Dysfunction in Type 1 Diabetes

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Abstract The DNA‐Dependent Protein Kinase catalytic subunit (DNA‐PKcs) acts as a principal executor in the DNA damage response (DDR), mediating phosphorylation of broad spectrum substrates integral to repair and apoptosis. This investigation seeks discern possible association mechanisms linking hyperglycemia‐induced ferroptosis DNA‐PKcs DCM. data exhibits substantial activation DNAPKcs‐ dependent DDR mice with streptozotocin‐induced However, deletion cardiomyocytes notably mitigates damage, enhances heart function dampens inflammatory response. Co‐IP/MS analysis subsequent validation experiments demonstrate that directly interacts phosphorylates YAP1 at Thr226. event facilitates nuclear retention YAP1, where it intensifies transcription ferroptosis‐associated genes. Knockin expressing nonphosphorylatable T226A mutant display decreased ferroptosis, reduced myocardial fibrosis improved function. Taken together, this study unravels an intracellular stress sensor, perceiving hyperglycemic conditions subsequently transmitting signal incite through interplay between YAP1. novel insight suggests DNA‐PKcs‐mediated could be promising therapeutic targets for management

Language: Английский

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Sirtuin1 Suppresses Calcium Oxalate Nephropathy via Inhibition of Renal Proximal Tubular Cell Ferroptosis Through PGC‐1α‐mediated Transcriptional Coactivation

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

Abstract Calcium oxalate (CaOx) crystals induce renal tubular epithelial cell injury and subsequent nephropathy. However, the underlying mechanisms remain unclear. In present study, single‐cell transcriptome sequencing is performed on kidney samples from mice with CaOx nephrocalcinosis. Renal proximal cells are identified as most severely damaged population accompanied by elevated ferroptosis. Further studies demonstrated that sirtuin1 (Sirt1) effectively reduced ferroptosis crystal‐induced in a glutathione peroxidase 4 (GPX4)‐dependent manner. Mechanistically, Sirt1 relies peroxisome proliferator‐activated receptor gamma coactivator 1α (PGC‐1α) to promote resistance epithelium, PGC‐1α can recruit nuclear factor erythroid 2‐related 2 (NRF2) promoter region of GPX4 co‐activate transcription. This work provides new insight into mechanism identifies potential preventative therapeutic targets for crystal nephropathies.

Language: Английский

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Ilexgenin A Alleviates Myocardial Ferroptosis in Response to Ischemia Reperfusion Injury via the SIRT1 Pathway

Phytotherapy Research, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 19, 2024

Myocardial ischemia-reperfusion (I/R) injury has emerged as an increasingly serious cardiovascular health concern worldwide, with ferroptosis playing a pivotal role the underlying pathogenic process. This study aimed to investigate pharmacological effect and mechanism of Ilexgenin A on cardiomyocyte induced by myocardial I/R injury. In vivo, we established murine anterior descending artery ligation/recanalization model evaluate cardioprotective A. Bioinformatics analysis, molecular docking, Surface Plasmon Resonance imaging were conducted predict targets vitro experiments, neonatal rat cardiomyocytes (NRCMs) utilized further explore in inhibiting using chemiluminescence immunofluorescence staining, electron microscopy, biochemical assay, RT-qPCR, western blotting, so on. The results showed that protected against cardiac dysfunction, ameliorated mitochondrial damage via silence information regulator 1 (SIRT1) pathway, trend was consistently observed NRCMs. Additionally, SIRT1 knockdown siRNA delivery partially abrogated beneficial effects ameliorating damage, then aggravated erastin-induced Overall, Our research demonstrated inhibition pathway one mechanisms which exerted effect.

Language: Английский

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SNX3 Promotes Doxorubicin-Induced Cardiomyopathy by Regulating GPX4-Mediated Ferroptosis

International Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 21(9), P. 1629 - 1639

Published: Jan. 1, 2024

The complete molecular mechanism underlying doxorubicin-induced cardiomyopathy remains incompletely elucidated. In this investigation, we engineered mice with cardiomyocyte-specific

Language: Английский

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