Ferroptosis: a novel mechanism of cell death in ophthalmic conditions

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 27, 2024

Ferroptosis, a new type of programmed cell death proposed in recent years, is characterized mainly by reactive oxygen species and iron-mediated lipid peroxidation differs from death, such as apoptosis, necrosis, autophagy. Ferroptosis associated with variety physiological pathophysiological processes. Recent studies have shown that ferroptosis can aggravate or reduce the occurrence development diseases targeting metabolic pathways signaling tumors, ischemic organ damage, other degenerative related to peroxidation. Increasing evidence suggests closely linked onset progression various ophthalmic conditions, including corneal injury, glaucoma, age-related macular degeneration, diabetic retinopathy, retinal detachment, retinoblastoma. Our review current research on reveals significant advancements our understanding pathogenesis, aetiology, treatment these conditions.

Language: Английский

---

Resveratrol alleviates reactive oxygen species and inflammation in diabetic retinopathy via SIRT1/HMGB1 pathway-mediated ferroptosis

Toxicology and Applied Pharmacology, Journal Year: 2024, Volume and Issue: 495, P. 117214 - 117214

Published: Dec. 22, 2024

Language: Английский

---

Targeting ion homeostasis in metabolic diseases: molecular mechanisms and targeted therapies

Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107579 - 107579

Published: Jan. 5, 2025

The incidence of metabolic diseases-hypertension, diabetes, obesity, dysfunction-associated steatotic liver disease (MASLD), and atherosclerosis-is increasing annually, imposing a significant burden on both human health the social economy. occurrence development these diseases are closely related to disruption ion homeostasis, which is crucial for maintaining cellular functions equilibrium. However, specific mechanism homeostasis in still unclear. This article reviews role pathogenesis assesses its potential as therapeutic target. Furthermore, explores pharmacological strategies that target channels transporters, including existing drugs emerging under development. Lastly, discusses direction future strategies, possibility gene therapy targeting personalized using novel biomarkers. In summary, provides new perspective approach treatment diseases.

Language: Английский

---

Sodium pump subunit NKAα1 protects against diabetic endothelial dysfunction by inhibiting ferroptosis through the autophagy‐lysosome degradation of ACSL4

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(2)

Published: Feb. 1, 2025

Language: Английский

---

Targeting Ferroptosis and Ferritinophagy Improves Tooth Extraction Socket Healing in Type 2 Diabetes Mellitus Via Human Bone Marrow Mesenchymal Stem Cells Modulation

Published: Jan. 1, 2025

Language: Английский

---

Metrnl Ameliorates Ferroptosis in Model of Diabetic Foot Ulcer Through the Inhibition of Mitochondrial Damage via LKB1/AMPK Signaling

Experimental and Clinical Endocrinology & Diabetes, Journal Year: 2025, Volume and Issue: 133(03), P. 120 - 132

Published: March 1, 2025

Abstract Diabetic foot ulcer (DFU) represents a severe complication of diabetes, mainly caused by peripheral vascular occlusion and infection, presenting significant clinical challenges in treatment potentially resulting gangrene, amputation, or even fatality. This study aimed to investigate the involvement underlying mechanisms Meteorin-like (Metrnl) pathogenic process DFU. Mice underwent diabetes induction streptozotocin, while human umbilical vein endothelial cells (HUVECs) were exposed 5.5, 10, 20 40 mM glucose. HUVECs transfected with negative Metrnl si-nc si-Metrnl plasmids via Lipofectamine 2000. The expression was down-regulated both patients murine model Elevated glucose levels diminished through enhanced ubiquitination. suppression exacerbated mouse alleviated oxidative stress ferroptosis DFU inhibiting mitochondrial damage. induced liver kinase B1 (LKB1)/AMP-activated protein (AMPK) signaling model. LKB1 attenuated effects on data cumulatively demonstrate that ameliorates damage LKB1/AMPK signaling, suggesting targeting may emerge as potential preventive approach against other diabetes.

Language: Английский

---

m6A demethylase ALKBH5 reduces ferroptosis in diabetic retinopathy through the m6A‐YTHDF1‐ACSL4 axis

Diabetic Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Abstract Aim Diabetic retinopathy (DR) represents the main ocular complication of diabetes. Targeting ferroptosis is a promising treatment choice for various diabetic complications. N6‐methyladenosine (m6A) demethylase alkylation repair homolog protein 5 (ALKBH5) functions as pivotal regulator ferroptosis, and we investigated its role molecular mechanisms in DR. Methods A DR mouse model was developed by streptozotocin (STZ) intraperitoneal injection. High glucose (HG)‐induced human retinal pigment epithelial cells (ARPE‐19) were used vitro . ALKBH5, YTH RNA binding 1 (YTHDF1) acyl‐CoA synthetase long‐chain family member 4 (ACSL4) expression levels examined RT‐qPCR Western blot. The biological ALKBH5 vivo gain‐of‐function loss‐of‐function analyses. ALKBH5's downstream regulatory detected bioinformatics analysis, pull‐down, MeRIP‐qPCR actinomycin D assay. Results under‐expressed while YTHDF1 ACSL4 up‐regulated tissues STZ‐induced mice HG‐stimulated ARPE‐19 cells. Ectopically expressed or knockdown partially reversed increased , evidenced decreased Fe 2+ malondialdehyde reactive oxygen species yet glutathione level. mediated m6A modification mRNA disrupted stability YTHDF1‐dependent manner. Importantly, data demonstrated that overexpression repressed alleviated down‐regulating ACSL4. Conclusion These findings suggest may delay progression reducing through m6A‐YTHDF1‐ACSL4 axis, offering therapeutic paradigms

Language: Английский

---

From bench to bedside: targeting ferroptosis and mitochondrial damage in the treatment of diabetic cardiomyopathy

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

Published: April 25, 2025

Diabetic cardiomyopathy (DCM) is a common and fatal cardiac complication caused by diabetes, with its pathogenesis involving various forms of cell death mitochondrial dysfunction, particularly ferroptosis injury. Recent studies have indicated that damage play crucial roles in the onset progression DCM, though their precise regulatory mechanisms remain unclear. Of particular interest interaction between damage, as well synergistic effects, which are not fully understood. This review summarizes injury DCM explores molecular involved, an emphasis on interplay these two processes. Additionally, article offers overview targeted drugs shown to be effective cellular experiments, animal models, clinical trials, analyzing action potential side effects. The goal provide insights for future drug development applications. Moreover, challenges prospects multi-target combination therapies personalized medicine interventions practice offer strategic guidance comprehensive prevention management DCM.

Language: Английский

---

Neutrophil extracellular traps induce fibroblast ferroptosis via IRE1α/XBP1-mediated ER stress to impair diabetic wound healing

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: 236, P. 17 - 27

Published: May 14, 2025

Language: Английский

---

Lipocalin-2-mediated ferroptosis as a target for protection against light-induced photoreceptor degeneration

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: May 15, 2025

Abstract Background Retinal degeneration is a leading cause of blindness worldwide. The induction ferroptosis has been identified as an important mechanism contributing to the loss photoreceptors in retinal degeneration. Lipocalin-2 (LCN2) exhibits iron-regulatory properties and may modulate cell viability various diseases. However, effects LCN2 on remain unclear. Methods A light-induced injury model using 661W photoreceptor cells male rat were established. protein expression was assessed by western blotting. vitro investigated recombinant (rLCN2) small-interfering RNA (siRNA) targeting (siLCN2). Fe 2+ , malondialdehyde (MDA), tripeptide glutathione (GSH) levels, ferroptosis-associated proteins (solute carrier family 7 member 11 [SLC7A11] peroxidase-4 [GPX4]) measured. phosphokinase array blotting performed elucidate mechanisms underlying LCN2-modulated ferroptosis. Additionally, protective knockdown adeno-associated virus (AAV)-expressing short hairpin (shRNA) (AAV-shRNA-LCN2) structure function vivo evaluated hematoxylin eosin staining electroretinography. Results significantly upregulated following light exposure. Treatment with rLCN2 induced cells, shown decreased viability, increased inhibition SLC7A11 GPX4 expression, depletion GSH, enhanced MDA whereas siLCN2 protected against these effects. Exposure activated c-Jun N-terminal kinase (JNK), administration JNK inhibitor SP600125 from Lastly, AAV-shRNA-LCN2 inhibited retina, vivo. Conclusion key regulator modulating pathway. Therefore, presents new target for treatment

Language: Английский

---