JAG1/Notch Pathway Inhibition Induces Ferroptosis and Promotes Cataractogenesis

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(1), С. 307 - 307

Опубликована: Янв. 1, 2025

Cataracts remain the leading cause of visual impairment worldwide, yet underlying molecular mechanisms, particularly in age-related cataracts (ARCs), are not fully understood. The Notch signaling pathway, known for its critical role various degenerative diseases, may also contribute to ARC pathogenesis, although specific involvement is unclear. This study investigates regulating ferroptosis lens epithelial cells (LECs) and impact on progression. RNA sequencing anterior capsule samples from patients revealed a significant downregulation signaling, coupled with an upregulation ferroptosis-related genes. Notch1 expression decreased, while markers increased age-dependent manner. In vitro, alleviated by decreasing ferritin heavy chain 1 (FTH1) p53 levels enhancing nuclear factor erythroid 2-related 2 (Nrf2), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11). Conversely, inhibition exacerbated ferroptosis, as evidenced reduced Nrf2, GPX4, SLC7A11 expression. These findings suggest that promotes LECs impairing Nrf2/GPX4 antioxidant thereby contributing development. offers new insights into pathogenesis highlights pathway potential therapeutic target preventing or mitigating

Язык: Английский

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Emodin protects against severe acute pancreatitis-associated acute lung injury by activating Nrf2/HO-1/GPX4 signal and inhibiting ferroptosis in vivo and in vitro

BMC Gastroenterology, Год журнала: 2025, Номер 25(1)

Опубликована: Фев. 5, 2025

Severe acute pancreatitis (SAP) has high morbidity, a complicated and dangerous course, many complications, including severe pulmonary complications. SAP-associated lung injury (SAP-ALI) is still significant challenge for surgeons because of its mortality. Therefore, more effective treatment methods are urgently needed. Emodin (EMO) shown tremendous potential in treating refractory diseases. However, protection mechanism SAP-ALI needs to be further clarified. This study was undertaken investigate the protective effects EMO against SAP rats alveolar epithelial cells, with particular focus on classical ferroptosis pathway. In an vivo study, forty SD were evenly split into five groups: sham operation (SO) group, biliopancreatic duct retrogradely injected 5% sodium taurocholate (STC) create + group administered via gavage following modeling, ML385 (a given inhibitor nuclear factor erythroid 2-related 2 (Nrf2)), group. vitro A549 cell lines exposed lipopolysaccharide (LPS) treated EMO. also used inhibit expression Nrf2. Pancreatic tissue damage evaluated using histological examination molecular experiments. Enzyme-linked immunosorbent assays (ELISA) assess levels pro-inflammatory cytokines, Fe2+, associated oxidative stress indicators serum supernatant. Real-time polymerase chain reaction (PCR), Western blot (WB), immunofluorescence find expressions related mRNAs proteins or cells. The findings demonstrated that suppressing Nrf2 exacerbated inflammatory response brought by pathological alterations SAP-ALI. reversed this change activating Nrf2/Heme Oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4) signal path. Moreover, these results showed EMO, contrary ML385, suppressed response, which manifested as up-regulated glutathione (GSH) GPX4 down-regulated malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS) levels. Our effectively inhibited both vitro, while modulating Nrf2/HO-1/GPX4 signaling pathway provide

Язык: Английский

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Oxidant-Based Cytotoxic Agents During Aging: From Disturbed Energy Metabolism to Chronic Inflammation and Disease Progression

Biomolecules, Год журнала: 2025, Номер 15(4), С. 547 - 547

Опубликована: Апрель 9, 2025

In humans, aging is an inevitable consequence of diminished growth processes after reaching maturity. The high order biomolecules in cells and tissues continuously disturbed by numerous physical chemical destructive impacts. Host-derived oxidant-based cytotoxic agents (reactive species, transition free metal ions, heme) contribute considerably to this damage. These are under the control immediately acting antagonizing principles, which important ensure cell tissue homeostasis. review, I apply concept host-derived their interplay with principles process. During aging, energy metabolism supply dioxygen nutrients increasingly disturbed. addition, a chronic inflammatory state develops, condition known as inflammaging. balance between protective mechanisms analyzed depending on age-based physiological alterations ATP production. Disturbances associated development age-related diseases comorbidities. An enhanced production reactive species from dysfunctional mitochondria, cellular redox homeostasis, adaptations hypoxia highlighted. Examples how disturbances pathogenesis persons advanced age given.

Язык: Английский

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Lespedeza bicolor Turcz. Honey Prevents Inflammation Response and Inhibits Ferroptosis by Nrf2/HO-1 Pathway in DSS-Induced Human Caco-2 Cells

Antioxidants, Год журнала: 2024, Номер 13(8), С. 900 - 900

Опубликована: Июль 25, 2024

Lespedeza bicolor Turcz. (L. bicolor) honey, a monofloral has garnered increased attention due to its origin in the L. plant. A previous study shown that honey can ameliorate inflammation. In this study, we aimed investigate effects of extract and biomarker (Trifolin) on DSS-induced ulcerative colitis (UC). Our results demonstrated Trifolin significantly expression levels tight junction cytokines Claudin-1 ZO-1. Additionally, they decreased pro-inflammatory factors TNF-α IL-6 enhanced antioxidant NQO1 GSTA1. Based metabolomic analyses, regulated progression UC by inhibiting ferroptosis. Mechanistically, improved SOD iron load, GSH/GSSG ratio, reduced MDA content ROS release, upregulated Nrf2/HO-1 pathway, thereby UC. Moreover, ferroptosis-related genes indicated FTL, ACSL4, PTGS2 while increasing SLC7A11 resist conclusion, our found improves ferroptosis activating pathway. These findings further elucidate understanding anti-inflammatory activities honey.

Язык: Английский

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Functional Relationships between L1CAM, LC3, ATG12, and Aβ

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(19), С. 10829 - 10829

Опубликована: Окт. 9, 2024

Abnormal protein accumulations in the brain are linked to aging and pathogenesis of dementia various types, including Alzheimer’s disease. These can be reduced by cell indigenous mechanisms. Among these is autophagy, whereby proteins transferred lysosomes for degradation. Autophagic dysfunction hampers elimination pathogenic aggregations that contribute death. We had observed adhesion molecule L1 interacts with microtubule-associated 1 light-chain 3 (LC3), which needed autophagy substrate selection. increases survival an LC3-dependent manner via its extracellular LC3 interacting region (LIR). also Aβ reduces plaque load AD model mouse. Based on results, we investigated whether could aggregated clearance. here show autophagy-related 12 (ATG12) LIR domain, whereas interaction ubiquitin-binding p62/SQSTM1 does not depend LIR. Aβ, bound L1, carried autophagosome leading elimination. Showing mitophagy-related L1-70 fragment ubiquitinated, expect pathway contributes propose enhancing functions may therapy humans.

Язык: Английский

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Heme Oxygenase‐1 Overexpression Activates the IRF1/DRP1 Signaling Pathway to Promote M2‐Type Polarization of Spinal Cord Microglia

Drug Development Research, Год журнала: 2024, Номер 85(8)

Опубликована: Дек. 1, 2024

Microglia-mediated neuroinflammatory responses have a critical function in the spinal cord injury (SCI) mechanism, and targeted modulation of microglia activity has emerged as new therapeutic strategy for SCI. Heme oxygenase 1(HO-1) regulates close dynamic crosstalk between oxidative stress inflammatory responses. This investigation aimed to study molecular pathways by which HO-1 response microglia. We cultivated primary rat BV2 cell lines used lipopolysaccharide (LPS) stimulate establish an vitro model. The adeno-associated virus (AAV) was induce overexpression observe effects on survival, morphological changes, activation, cytokines secretion, mitochondrial dynamics, nucleotide-binding oligomerization domain-like receptor protein (NLRP3) complex nuclear factor-κB (NF-κB) signaling pathways. It found that successfully induced using AAV vitro. increased survival reduced apoptosis microenvironment. Overexpressed inhibited M1-type polarization, downregulated NF-κB pathway, NLRP3 secretion factors. maintained stability dynamics excessive cleavage. Further experiments showed activated interferon regulatory factor 1 (IRF1)/dynamin-related (DRP1) thereby promoting M2-type polarization improving neuronal survival. demonstrates activates IRF1/DRP1 axis, M2 attenuating neuroinflammation suppressing pathway. These outcomes offer visions important clues effectively managing SCI clinic.

Язык: Английский

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Ferroptosis is involved in the damage of ocular lens under long-term PM2.5 exposure in rat models and humans

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 288, С. 117397 - 117397

Опубликована: Ноя. 28, 2024

Язык: Английский

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