Glucocorticoid triggers endothelial cell ferroptosis via NOX4-mediated reactive oxygen species and lipid peroxidation DOI Creative Commons
Lijun Fang, Jiazheng Chen, Wenqiang Li

et al.

Emergency and Critical Care Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Abstract Background Glucocorticoids (GCs) are widely used in acute and critical illnesses, but long-term high-dose use of GCs can cause several vascular side effects. However, the underlying mechanisms not well-understood. Ferroptosis, a novel form reactive oxygen species (ROS)-dependent cell death, is characterized by intracellular iron accumulation lipid peroxidation. NADPH oxidase 4 (NOX4) major source ROS. The roles ferroptosis NOX4 GC-induced endothelial injury remain unknown. Methods Human umbilical vein cells (HUVECs) were exposed to varying concentrations dexamethasone (DEX) evaluate expression. Further mechanistic studies conducted using NOX4-overexpressing adenovirus (Ad-NOX4), small interfering RNA (siRNA), ferrostatin-1 (FER-1), erastin. Results Our findings demonstrate that DEX induces HUVECs. Inhibition with FER-1 prevents DEX-induced reduction HUVEC viability. Furthermore, treatment increases expression HUVECs, overexpression Ad-NOX4 promotes ferroptosis. knockdown siRNA suppresses ROS production, peroxidation, ferroptosis, thereby improving viability, angiogenesis, migration capacity DEX-treated protective effect negated reactivation Conclusion occurs through NOX4-mediated production leading impaired dysfunction. ameliorate damage

Language: Английский

Unraveling the dual role of bilirubin in neurological Diseases: A Comprehensive exploration of its neuroprotective and neurotoxic effects DOI
Arshdeep Kaur,

Rohit,

Khadga Raj Aran

et al.

Brain Research, Journal Year: 2025, Volume and Issue: unknown, P. 149472 - 149472

Published: Jan. 1, 2025

Language: Английский

Citations

2
Oxidative Stress and Redox Imbalance: Common Mechanisms in Cancer Stem Cells and Neurodegenerative Diseases DOI Creative Commons

Nikhil Raj Selvaraj,

Durga Nandan,

B J Bipin Nair

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 511 - 511

Published: March 29, 2025

Oxidative stress (OS) is an established hallmark of cancer and neurodegenerative disorders (NDDs), which contributes to genomic instability neuronal loss. This review explores the contrasting role OS in stem cells (CSCs) NDDs. Elevated levels reactive oxygen species (ROS) contribute promote tumor initiation progression CSCs, while NDDs such as Alzheimer’s Parkinson’s disease, accelerates death impairs cellular repair mechanisms. Both scenarios involve disruption delicate balance between pro-oxidant antioxidant systems, leads chronic oxidative stress. Notably, CSCs neurons display alterations redox-sensitive signaling pathways, including Nrf2 NF-κB, influence cell survival, proliferation, differentiation. Mitochondrial dynamics further illustrate these differences: enhanced function supports adaptability whereas impairments heighten vulnerability. Understanding common mechanisms OS-induced redox imbalance may provide insights for developing interventions, addressing aging hallmarks, potentially mitigating or preventing both

Language: Английский

Citations

2
Tubular CD44 plays a key role in aggravating AKI through NF-κB p65-mediated mitochondrial dysfunction DOI Creative Commons

Jiewu Huang,

Ping Meng, Liang Ye

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 20, 2025

Acute kidney injury (AKI) is in rapid prevalence nowadays. Of note, the underlying mechanisms have not been clarified. Several reports showed a cluster of differentiation-44 (CD44), cell-surface glycoprotein, might be involved AKI. However, its role AKI has clearly Herein, we found CD44 increased renal tubules mice. Gene ablation improved mitochondrial biogenesis and fatty acid oxidation (FAO) function, further protecting against tubular cell death injury. Conversely, ectopic impaired homeostasis exacerbated apoptosis to aggravate progression. From transcriptome sequencing, that induces mitogen-activated protein kinase (MAPK) NF-κB p65 signaling. Lipidomics also interfered with multiple aspects lipid metabolism. We deeply investigated inhibited transcription peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), resulting dysfunction apoptosis. facilitated iron intake assist ferroptosis. Hence, our study provided new mechanism for AKI, demonstrated targeted inhibition on could promising therapeutic strategy resist

Language: Английский

Citations

1
Glucocorticoid triggers endothelial cell ferroptosis via NOX4-mediated reactive oxygen species and lipid peroxidation DOI Creative Commons
Lijun Fang, Jiazheng Chen, Wenqiang Li

et al.

Emergency and Critical Care Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Abstract Background Glucocorticoids (GCs) are widely used in acute and critical illnesses, but long-term high-dose use of GCs can cause several vascular side effects. However, the underlying mechanisms not well-understood. Ferroptosis, a novel form reactive oxygen species (ROS)-dependent cell death, is characterized by intracellular iron accumulation lipid peroxidation. NADPH oxidase 4 (NOX4) major source ROS. The roles ferroptosis NOX4 GC-induced endothelial injury remain unknown. Methods Human umbilical vein cells (HUVECs) were exposed to varying concentrations dexamethasone (DEX) evaluate expression. Further mechanistic studies conducted using NOX4-overexpressing adenovirus (Ad-NOX4), small interfering RNA (siRNA), ferrostatin-1 (FER-1), erastin. Results Our findings demonstrate that DEX induces HUVECs. Inhibition with FER-1 prevents DEX-induced reduction HUVEC viability. Furthermore, treatment increases expression HUVECs, overexpression Ad-NOX4 promotes ferroptosis. knockdown siRNA suppresses ROS production, peroxidation, ferroptosis, thereby improving viability, angiogenesis, migration capacity DEX-treated protective effect negated reactivation Conclusion occurs through NOX4-mediated production leading impaired dysfunction. ameliorate damage

Language: Английский

Citations

0