DNA‐PKcs‐Driven YAP1 Phosphorylation and Nuclear Translocation: a Key Regulator of Ferroptosis in Hyperglycemia‐Induced Cardiac Dysfunction in Type 1 Diabetes DOI Creative Commons
Junyan Wang, Xing Chang, Chun Li

et al.

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

Targeting Ferroptosis and Ferritinophagy Improves Tooth Extraction Socket Healing in Type 2 Diabetes Mellitus Via Human Bone Marrow Mesenchymal Stem Cells Modulation DOI
Yifeng Bian, Jianfeng Li, Fan Xu

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0

Potential therapeutic targets for Alzheimer’s disease: Fibroblast growth factors and their regulation of ferroptosis, pyroptosis and autophagy DOI
Yiwei Li,

Chenbo Yang,

Xiaonan Liu

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0

Exploring the key target molecules of angiogenesis in diabetic cardiomyopathy based on bioinformatics analysis DOI Creative Commons

Fengli Hu,

Ruixue Guo,

Yaxin Zhi

et al.

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: April 17, 2025

Diabetic cardiomyopathy has a very high incidence and serious clinical consequences, making it an urgent problem to be solved. Angiogenesis is significant phenotype in the occurrence development of diabetic cardiomyopathy, especially damage angiogenesis cardiac microvessels, which inextricably linked risk patients. In current basic research, there still lack treatment methods that directly target cardiomyopathy. This study hopes discover key molecules related damage, provide ideas for possible interventions. Sequencing data animals cells were obtained from GEO database, differentially expressed genes analyzed. Subsequently, angiogenesis-related clustered functional pathway analysis. Then, microangiogenesis mice changes glucose-stimulated HUVECs verified, top three verified using western blot. 24 associated with found GSE241565(human) GSE215979(mice). Among them, 11 showed same trend two databases. Then CD31 staining hearts microvascular was impaired, decreased tube formation, wound healing migration weakened. Finally, 3 most no difference between Edn1 Lepr. At time, Efnb2 significantly increased under glucose stimulation. Combined sequencing animal cell models differential screened. These findings not only elucidate novel molecular axis linking but also highlight as potential therapeutic target.

Language: Английский

Citations

0

Low dose of micro-/nano-plastics mixture induced cardiac hypertrophy and reductive stress: the liver-heart crosstalk and hepatic-cardiac organoids-on-a-chip DOI
Wei Cheng,

Hange Chen,

Yue Zhou

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: 490, P. 137686 - 137686

Published: Feb. 20, 2025

Language: Английский

Citations

0

Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects DOI Creative Commons
Qin Ru, Yusheng Li, Feng Zhang

et al.

Bone Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 25, 2025

Abstract The muscular system plays a critical role in the human body by governing skeletal movement, cardiovascular function, and activities of digestive organs. Additionally, muscle tissues serve an endocrine function secreting myogenic cytokines, thereby regulating metabolism throughout entire body. Maintaining requires iron homeostasis. Recent studies suggest that disruptions ferroptosis, form iron-dependent cell death, are essential contributors to progression wide range diseases disorders, including sarcopenia, cardiomyopathy, amyotrophic lateral sclerosis. Thus, comprehensive overview mechanisms ferroptosis these conditions is crucial for identifying potential therapeutic targets developing new strategies disease treatment and/or prevention. This review aims summarize recent advances understanding molecular underlying context injury, as well associated disorders. Moreover, we discuss within pathway possible managing Finally, shed light on current limitations future prospects interventions targeting ferroptosis.

Language: Английский

Citations

0

Aerobic Exercise Activates Fibroblast Growth Factor 21 and Alleviates Cardiac Ischemia/Reperfusion-induced Neuronal Oxidative Stress and Ferroptosis in Paraventricular Nucleus DOI
Yanru Zhao, Lili Feng, Chenyang Wu

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Language: Английский

Citations

0

DNA‐PKcs‐Driven YAP1 Phosphorylation and Nuclear Translocation: a Key Regulator of Ferroptosis in Hyperglycemia‐Induced Cardiac Dysfunction in Type 1 Diabetes DOI Creative Commons
Junyan Wang, Xing Chang, Chun Li

et al.

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

Citations

0