Panaxydol attenuates ferroptosis against LPS-induced acute lung injury in mice by Keap1-Nrf2/HO-1 pathway

Journal of Translational Medicine, Год журнала: 2021, Номер 19(1)

Опубликована: Март 2, 2021

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induces uncontrolled and self-amplified pulmonary inflammation, has high morbidity mortality rates in critically ill patients. In recent years, many bioactive ingredients extracted from herbs have been reported to effectively ameliorate ALI/ARDS via different mechanisms. Ferroptosis, categorized as regulated necrosis, is more immunogenic than apoptosis contributes the progression of ALI. this study, we examined impact panaxydol (PX), isolated roots Panax ginseng, on lipopolysaccharide (LPS)-induced ALI mice.In vivo, role PX LPS-induced mice was tested by determination edema ferroptosis. vitro, BEAS-2B cells were used investigate molecular mechanisms which functions ferroptosis their relationship.Administration protected against ALI, including significantly ameliorated pathological changes, decreased extent edema, inhibited inflammation bronchial epithelial cell line cells. The relationship between investigated. results showed that mediated LPS-treated cells, might inhibiting Meanwhile, could upregulate Keap1-Nrf2/HO-1 pathway, selective inhibition pathway abolished anti-ferroptotic anti-inflammatory cells.PX attenuates a promising novel therapeutic candidate for

Язык: Английский

---

Ferritinophagy and ferroptosis in the management of metabolic diseases

Trends in Endocrinology and Metabolism, Год журнала: 2021, Номер 32(7), С. 444 - 462

Опубликована: Май 15, 2021

Язык: Английский

---

Rehmannioside A improves cognitive impairment and alleviates ferroptosis via activating PI3K/AKT/Nrf2 and SLC7A11/GPX4 signaling pathway after ischemia

Journal of Ethnopharmacology, Год журнала: 2022, Номер 289, С. 115021 - 115021

Опубликована: Янв. 26, 2022

Язык: Английский

---

Neutrophil extracellular traps mediate m⁶A modification and regulates sepsis-associated acute lung injury by activating ferroptosis in alveolar epithelial cells

International Journal of Biological Sciences, Год журнала: 2022, Номер 18(8), С. 3337 - 3357

Опубликована: Янв. 1, 2022

Neutrophil extracellular traps (NETs) production is a major strategy employed by polymorphonuclear neutrophils (PMNs) to fight against microbes. NETs have been implicated in the pathogenesis of various lung injuries, although few studies explored sepsis-associated acute injury (SI-ALI). Here, we demonstrate contribution pathology ALI inducing ferroptosis alveolar epithelial cells. Using both vitro and vivo studies, our findings show enhanced accumulation patients mice, as well closely related upregulation ferroptosis, induction which depends on METTL3-induced m6A modification GPX4. CLP-induced mouse model established with METTL3-/- versus WT addition METTL3 knockout overexpression vitro, elucidated confirmed critical role NETs-induced ALI. These support for subsequent

Язык: Английский

---

The gut microbiota metabolite capsiate promotes Gpx4 expression by activating TRPV1 to inhibit intestinal ischemia reperfusion-induced ferroptosis

Gut Microbes, Год журнала: 2021, Номер 13(1)

Опубликована: Янв. 1, 2021

Ferroptosis, a new type of cell death has been found to aggravate intestinal ischemia/reperfusion (I/R) injury. However, little is known about the changes gut microbiota and metabolites in I/R role on ferroptosis-induced This study aimed establish mouse model ileum organoid hypoxia/reoxygenation (H/R) explore during protective ability capsiate (CAT) against ferroptosis-dependent Intestinal induced disturbance significant metabolites. We that CAT metabolite levels preoperative stool patients undergoing cardiopulmonary bypass were negatively correlated with Furthermore, reduced injury vivo vitro. effects abolished by RSL3, an inhibitor glutathione peroxidase 4 (Gpx4), which negative regulator ferroptosis. also promote Gpx4 expression inhibit was abrogated JNJ-17203212, antagonist transient receptor potential cation channel subfamily V member 1 (TRPV1). suggests enhances inhibits ferroptosis activating TRPV1 injury, providing avenue for management

Язык: Английский

---

Dexmedetomidine attenuates myocardial ischemia/reperfusion-induced ferroptosis via AMPK/GSK-3β/Nrf2 axis

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 154, С. 113572 - 113572

Опубликована: Авг. 18, 2022

The present study aimed to investigate whether dexmedetomidine (Dex) exerts cardioprotection effect through inhibiting ferroptosis. Myocardial ischemia/reperfusion injury (MIRI) was induced in Sprague-Dawley rats Langendorff preparation. hemodynamic parameters were recorded. Triphenyltetrazolium chloride (TTC) staining used determine infarct size. In the vitro study, model of hypoxia/reoxygenation (HR) established H9c2 cells. Cell viability and apoptosis detected using cell counting kit 8 (CCK-8), AV/PI dual respectively. Lipid peroxidation as measured by fluorescence fatty acid analog C11-BODIPY581/591 probe intracellular ferrous iron levels Phen Green SK (PGSK) probe, whereas immunofluorescence transmission electron microscopy also examine Protein investigated Western blot. interactions AMPK/GSK-3β signaling with Nrf2 assessed AMPK inhibition GSK-3β overexpression. Our findings indicated that Dex significantly alleviated myocardial infarction, improved heart function, decreased HR-induced accumulation Fe2+ lipid cardiomyocytes. increased expression Nrf2, SLC7A11, GPX4. However, ML385 blunted protective HR-treated Inhibition a specific inhibitor or siRNA phosphorylation Dex. Overexpression resulted lower nuclear depression enhanced expressions Nrf2. conclusion, protects hearts against MIRI-induced ferroptosis via activation pathway.

Язык: Английский

---

Nrf2 and STAT3 Alleviates Ferroptosis-Mediated IIR-ALI by Regulating SLC7A11

Oxidative Medicine and Cellular Longevity, Год журнала: 2020, Номер 2020, С. 1 - 16

Опубликована: Сен. 19, 2020

Acute lung injury (ALI) has gained increased attention in the field of critical illness research and is associated with a fatality rate approximately 50%. Nuclear factor erythroid 2-related factor2 ( Nrf2 ) key regulator intracellular oxidation homeostasis also functions as an antioxidant. It been reported that antioxidant stress closely related to ferroptosis inhibition. Signal transducer activator transcription 3 (STAT3) activated into phosphorylated STAT3 (pSTAT3) response tissue damage serves warning signal enhance inflammatory response. In this study, intestinal ischemia/reperfusion-induced acute (IIR-ALI) model was established C57BL/6 mice investigate role regulating IIR-ALI-associated ferroptosis. Compared those IIR-ALI group, injection Fe (15 mg/kg) or ferrostatin-1 (5 (ferroptosis promoter inhibitor, respectively) via tail vein could aggravate alleviate pulmonary edema, respectively. promoted phosphorylation amplify downstream signals. An vitro oxygen-glucose deprivation reoxygenation (OGD-R) MLE12 cells imitate ischemia/reperfusion condition. The were transfected lentiviruses increase downregulate levels STAT3. We found played roles by SLC7A11, which improved pathological processes ALI.

Язык: Английский

---

Molecular mechanisms of ferroptosis and relevance to inflammation

Inflammation Research, Год журнала: 2022, Номер 72(2), С. 281 - 299

Опубликована: Дек. 19, 2022

Язык: Английский

---

miR-125b-5p in adipose derived stem cells exosome alleviates pulmonary microvascular endothelial cells ferroptosis via Keap1/Nrf2/GPX4 in sepsis lung injury

Redox Biology, Год журнала: 2023, Номер 62, С. 102655 - 102655

Опубликована: Март 9, 2023

Sepsis is a fatal disease with high rate of morbidity and mortality, during which acute lung injury the earliest most serious complication. Injury pulmonary microvascular endothelial cells (PMVECs) induced by excessive inflammation plays an important role in sepsis injury. This study meant to explore protective effect mechanism ADSCs exosomes on PMVECs injury.We successfully isolated exosomes, characteristic were confirmed. reduced inflammatory response ROS accumulation cell PMVECs. Besides, inhibited ferroptosis while upregulated expression GPX4 And further inhibition experiments revealed that alleviated via upregulating GPX4. Meanwhile, could increase nucleus translocation Nrf2, decrease Keap1. miRNA analysis verified specific delivery miR-125b-5p Keap1 ferroptosis. In CLP model, relieve tissue death rate. oxidative stress tissue, remarkably Nrf2 GPX4.Collectively, we illustrated novel potentially therapeutic alleviate regulating Keap1/Nrf2/GPX4 expression, hence improve sepsis.

Язык: Английский

---

Targeting Ferroptosis: Pathological Mechanism and Treatment of Ischemia‐Reperfusion Injury

Oxidative Medicine and Cellular Longevity, Год журнала: 2021, Номер 2021(1)

Опубликована: Янв. 1, 2021

Ischemia‐reperfusion (I/R) is a pathological process that occurs in many organs and diseases. Reperfusion, recovery of blood flow, reoxygenation often lead to reperfusion injury. Drug therapy early can reduce tissue injury cell necrosis caused by ischemia, leading irreversible I/R Ferroptosis was clearly defined 2012 as newly discovered iron‐dependent, peroxide‐driven, nonapoptotic form regulated death. considered the cause This discovery provides new avenues for recognition treatment key factor leads organ failure. Given important role ferroptosis injury, there considerable interest potential targeted wide range injury‐related Recently, substantial progress has been made applying various The development regulators expected provide opportunities Herein, we analytically review mechanism related diseases from perspectives myocardial cerebral ischemic renal

Язык: Английский

---