Targeting hypoxia-inducible factor-1 in a hypoxidative stress model of age-related macular degeneration protects RPE cells from cell death and metabolic dysregulation DOI
Yoshiyuki Henning,

A. Schubert,

M Silva

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 17, 2024

Abstract Although age-related macular degeneration (AMD) is the most common blinding disease in elderly population, there are still many unknowns pathophysiology of this disease. This also reflected by a lack convincing treatment options against subtype, dry AMD. Oxidative stress and hypoxia retinal pigment epithelium (RPE) hallmarks Previously, we have shown that combination these two risk factors, i.e. hypoxidative stress, exacerbates RPE cell death ferroptosis. Hypoxia leads to stabilization hypoxia-inducible factors (HIFs), key regulators cellular adaptation hypoxic conditions. In present study, therefore investigated roles HIF-1 HIF-2 on human line under stress. For purpose, conducted siRNA-mediated knockdowns α-subunits HIF-2. We found especially iron metabolism was affected HIF-1α silencing, resulting decreased levels ferroptosis susceptibility. Surprisingly, heme oxygenase 1 (HO-1) superoxide dismutase 2 (SOD2) contributed death. observed metabolism, which usually impaired AMD cells, improved silencing. Furthermore, identified an FDA-approved small molecule inhibitor, Vorinostat, fully rescue cells from stress-induced conclusion, study highlights importance considering targeted HIF inhibition as promising approach for treating degeneration.

Language: Английский

Hypoxia induces ferroptotic cell death mediated by activation of the inner mitochondrial membrane fission protein MTP18/Drp1 in invertebrates DOI Creative Commons
Jiaqi Liu,

Xichao Sun,

Yijie Wu

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108326 - 108326

Published: Feb. 1, 2025

Hypoxia and ischemia damage sensitive organelles such as mitochondria, thus mitochondrial dysfunction contributes to metabolic disorders in crustaceans under hypoxia. The mechanisms associated with ferroptosis hypoxic have not been determined crustaceans. In particular, the early molecular events of dynamics require clarification. this study, two evolutionarily conserved fission proteins, Drp1 MTP18, were identified oriental river prawn (Macrobrachium nipponense). vitro, ferroptosis-mediated impairment membrane potential was induced by hypoxia hemocytes. hypoxia-induced hemocytes, activation increased phosphorylation at S616 identified. translocation also increased, fusion-related protein expression decreased vivo. Altered fission-fusion linked dysfunction, inducing a classic mechanism. Marf overexpression or knockdown protected against ferroptotic cell death vitro. Furthermore, verified be driven Drp1/MTP18 interaction. Under hypoxia, MTP18 transcription binding activated HIF-1α response elements (HREs) its promoter. Conjointly, resulted less apoptosis mortality gill tissue vitro; suggesting that adaptation involves vital function MTP18. conclusion, we uncovered role death. Therefore, suggest specific modulation MTP18/DRP1-mediated might therapeutic strategy stress-induced injury invertebrates.

Language: Английский

Citations

1
Propofol alleviates ropivacaine-induced neurotoxicity through the MALAT1/EZH2/BDNF axis DOI
Xiaoqing Liu,

Chun Chen

Molecular & Cellular Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Language: Английский

Citations

0
Folic Acid Promotes Peripheral Nerve Injury Repair via Regulating DNM3-AKT Pathway Through Mediating Methionine Cycle Metabolism DOI Creative Commons

Weibo Kang,

Yanli Zhang,

Wei Cui

et al.

NeuroMolecular Medicine, Journal Year: 2025, Volume and Issue: 27(1)

Published: March 31, 2025

Emerging evidence suggests that folic acid (FA) supports nerve repair, but its beneficial effects in peripheral injury (PNI) remains unclear. This study aims to investigate protective of FA against PNI and the underlying molecular mechanisms. High-performance liquid chromatography-tandem mass spectrometry was utilized for precise quantification metabolites. A sciatic crush model established rats, followed by assessments cell proliferation, apoptosis, motor function using CCK-8 assays, flow cytometry, balance beam test, respectively. Neuromorphological observations, electromyography, ELISA were conducted evaluate structural, electrophysiological, biochemical parameters. In vitro, restored methionine cycle Schwann cells neurons disrupted enzyme inhibition, improving viability, reducing preserving cellular structure. vivo, supplementation S-adenosylmethionine homocysteine levels a metabolism disorder enhanced function, neural morphology, neuron survival, electrophysiological recovery after PNI. Epigenetic analyses revealed modulated DNA methylation histone modifications DNM3 promoter, influencing gene expression. Furthermore, facilitated repair via DNM3-AKT pathway, regulating autophagy, oxidative stress-related enzymes. These findings highlight FA's potential promoting through metabolic epigenetic

Language: Английский

Citations

0
Exosomes From Muscle‐Derived Stem Cells Repair Peripheral Nerve Injury by Inhibiting Ferroptosis via the Keap1‐Nrf2‐Ho‐1 Axis DOI
Z Liu, Xiangyu Zeng, Wei Bian

et al.

Journal of Cellular Biochemistry, Journal Year: 2024, Volume and Issue: 125(8)

Published: June 17, 2024

Currently, the clinical outcomes of peripheral nerve injuries are suboptimal, highlighting urgent need to understand mechanisms injury enhance treatment strategies. Muscle-derived stem cells (MDSCs) a diverse group multipotent that hold promise for regeneration due their strong antioxidant and regenerative properties. Our research has revealed severe ferroptosis occurs in sciatic ipsilateral dorsal root ganglion following injury. Interestingly, we have observed MDSC-derived exosomes effectively suppress cell viability Schwann cells. Treatment with led increased expression BDNF P62 cells, decreased Keap1, Nrf2, HO-1 upregulated Rats treated exhibited improvements function, sensitivity stimuli, reduced muscle atrophy, indicating positive impact on post-injury recovery. In conclusion, our findings demonstrate occurrence post-injury, MDSC offering potential therapeutic strategy by inhibiting ferroptosis, activating Keap1-Nrf2-HO-1 pathway, optimizing repair environment.

Language: Английский

Citations

2
Ciprofol Ameliorates Myocardial Ischemia/Reperfusion Injury by Inhibiting Ferroptosis Through Upregulating HIF-1α DOI Creative Commons

Jun Ding,

Biying Wang, Yufan Yang

et al.

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 6115 - 6132

Published: Dec. 1, 2024

Ciprofol is a novel intravenous anesthetic that has been increasingly used in clinical anesthesia and sedation. Studies suggested ciprofol reduced oxidative stress inflammatory responses to alleviate cerebral ischemia/reperfusion (I/R) injury, but whether protects the heart against I/R injury mechanisms are unknown. Herein, we assessed effects of on ferroptosis during myocardial injury.

Language: Английский

Citations

2
Fighting ferroptosis: Protective effects of dexmedetomidine on vital organ injuries DOI

Lei Tian,

Qian Liu,

Xing Wang

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 354, P. 122949 - 122949

Published: Aug. 8, 2024

Language: Английский

Citations

1
The Influence of Anesthesia on Neuromonitoring During Scoliosis Surgery: A Systematic Review DOI Creative Commons
Małgorzata Domagalska, Tomasz Reysner, Piotr Janusz

et al.

NeuroSci, Journal Year: 2024, Volume and Issue: 5(4), P. 693 - 712

Published: Dec. 17, 2024

Background: Intraoperative neuromonitoring (IONM) is crucial for the safety of scoliosis surgery, providing real-time feedback on spinal cord and nerve function, primarily through motor-evoked potentials (MEPs). The choice anesthesia plays a role in influencing quality reliability these signals. This systematic review evaluates how different anesthetic techniques—total intravenous (TIVA), volatile anesthetics, regional approaches such as Erector Spinae Plane Block (ESPB), spinal, epidural anesthesia—affect IONM during surgery. Methods: A was conducted following PRISMA guidelines. PubMed, MEDLINE, EMBASE, Cochrane databases were searched studies published between 2017 2024 that examined impact techniques focus reporting MEP outcomes, protocols, postoperative neurological analgesic effects. Results: search initially identified 998 articles. After applying inclusion criteria based relevance, recency, methodological quality, citation frequency, 45 selected detailed review. Conclusion: erector (ESPB) provides distinct benefits over particularly maintaining accuracy, reducing hemodynamic instability, minimizing complications. ESPB’s ability to deliver effective segmental analgesia without compromising motor function makes it safer more efficient option pain management, enhancing patient outcomes.

Language: Английский

Citations

1
The Role of Ferroptosis in Amyotrophic Lateral Sclerosis Treatment DOI
Le Yi Wang, Lei Zhang,

Xin Yue Bai

et al.

Neurochemical Research, Journal Year: 2024, Volume and Issue: 49(10), P. 2653 - 2667

Published: June 12, 2024

Language: Английский

Citations

0
Targeting hypoxia-inducible factor-1 in a hypoxidative stress model of age-related macular degeneration protects RPE cells from cell death and metabolic dysregulation DOI
Yoshiyuki Henning,

A. Schubert,

M Silva

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 17, 2024

Abstract Although age-related macular degeneration (AMD) is the most common blinding disease in elderly population, there are still many unknowns pathophysiology of this disease. This also reflected by a lack convincing treatment options against subtype, dry AMD. Oxidative stress and hypoxia retinal pigment epithelium (RPE) hallmarks Previously, we have shown that combination these two risk factors, i.e. hypoxidative stress, exacerbates RPE cell death ferroptosis. Hypoxia leads to stabilization hypoxia-inducible factors (HIFs), key regulators cellular adaptation hypoxic conditions. In present study, therefore investigated roles HIF-1 HIF-2 on human line under stress. For purpose, conducted siRNA-mediated knockdowns α-subunits HIF-2. We found especially iron metabolism was affected HIF-1α silencing, resulting decreased levels ferroptosis susceptibility. Surprisingly, heme oxygenase 1 (HO-1) superoxide dismutase 2 (SOD2) contributed death. observed metabolism, which usually impaired AMD cells, improved silencing. Furthermore, identified an FDA-approved small molecule inhibitor, Vorinostat, fully rescue cells from stress-induced conclusion, study highlights importance considering targeted HIF inhibition as promising approach for treating degeneration.

Language: Английский

Citations

0