Energy stress modulation of AMPK/FoxO3 signaling inhibits mitochondria-associated ferroptosis DOI Creative Commons

Sufang Zhong,

Wenjin Chen,

Bocheng Wang

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 63, P. 102760 - 102760

Published: May 23, 2023

Cancer cells and ischemic diseases exhibit unique metabolic responses adaptations to energy stress. Forkhead box O 3a (FoxO3a) is a transcription factor that plays an important role in cell metabolism, mitochondrial dysfunction oxidative stress response. Although the AMP-activated protein kinase (AMPK)/FoxO3a signaling pathway pivotal maintaining homeostasis under conditions of stress, AMPK/FoxO3a mitochondria-associated ferroptosis has not yet been fully elucidated. We show glucose starvation induced activation inhibited by erastin. Inhibition AMPK or loss FoxO3a cancer condition can sensitize these ferroptosis. Glucose deprivation mitochondria-related gene expression, reduced DNA(mtDNA) copy number, decreased expression proteins lowered levels respiratory complexes inducing FoxO3a. Loss promoted membrane potential hyperpolarization, oxygen consumption, lipid peroxide accumulation abolished protective effects on vitro. In addition, we identified FDA-approved antipsychotic agent, potent agonist trifluoperazine, which largely ferroptosis-associated cerebral ischemia-reperfusion (CIR) injuries rats through AMPK/FoxO3a/HIF-1α mitochondria-dependent mechanisms. found binds promoters SLC7A11 reduces CIR-mediated glutamate excitotoxicity inhibiting SLC7A11. Collectively, results suggest modulation regulates activity alters The regulation may play crucial controls balance confers resistance CIR injuries.

Language: Английский

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

Jiucui Li,

Kongmiao Lu,

Fenglan Sun

et al.

Journal of Translational Medicine, Journal Year: 2021, Volume and Issue: 19(1)

Published: March 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

Language: Английский

Citations

314
Ferritinophagy and ferroptosis in the management of metabolic diseases DOI
Amir Ajoolabady,

Hamid Aslkhodapasandhokmabad,

Peter Libby

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2021, Volume and Issue: 32(7), P. 444 - 462

Published: May 15, 2021

Language: Английский

Citations

244
Rehmannioside A improves cognitive impairment and alleviates ferroptosis via activating PI3K/AKT/Nrf2 and SLC7A11/GPX4 signaling pathway after ischemia DOI

Chen Fu,

Yifan Wu,

Shaojiao Liu

et al.

Journal of Ethnopharmacology, Journal Year: 2022, Volume and Issue: 289, P. 115021 - 115021

Published: Jan. 26, 2022

Language: Английский

Citations

214
Neutrophil extracellular traps mediate m6A modification and regulates sepsis-associated acute lung injury by activating ferroptosis in alveolar epithelial cells DOI Creative Commons
Hao Zhang, Jinlong Liu, Yilu Zhou

et al.

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(8), P. 3337 - 3357

Published: Jan. 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

Language: Английский

Citations

196
The gut microbiota metabolite capsiate promotes Gpx4 expression by activating TRPV1 to inhibit intestinal ischemia reperfusion-induced ferroptosis DOI Creative Commons

Fan Deng,

Bing-Cheng Zhao, Xiao Yang

et al.

Gut Microbes, Journal Year: 2021, Volume and Issue: 13(1)

Published: Jan. 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

Language: Английский

Citations

178
Dexmedetomidine attenuates myocardial ischemia/reperfusion-induced ferroptosis via AMPK/GSK-3β/Nrf2 axis DOI Open Access
Zhuoran Wang,

Mengran Yao,

Leyu Jiang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 154, P. 113572 - 113572

Published: Aug. 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.

Language: Английский

Citations

178
Nrf2 and STAT3 Alleviates Ferroptosis-Mediated IIR-ALI by Regulating SLC7A11 DOI Creative Commons

Zhuanzhuan Qiang,

Hui Dong, Yangyang Xia

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 16

Published: Sept. 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.

Language: Английский

Citations

174
Molecular mechanisms of ferroptosis and relevance to inflammation DOI Open Access

Liyan Deng,

Shasha He,

Nuoqing Guo

et al.

Inflammation Research, Journal Year: 2022, Volume and Issue: 72(2), P. 281 - 299

Published: Dec. 19, 2022

Language: Английский

Citations

152
miR-125b-5p in adipose derived stem cells exosome alleviates pulmonary microvascular endothelial cells ferroptosis via Keap1/Nrf2/GPX4 in sepsis lung injury DOI Creative Commons

Kuo Shen,

Xujie Wang, Yunwei Wang

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 62, P. 102655 - 102655

Published: March 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.

Language: Английский

Citations

152
Targeting Ferroptosis: Pathological Mechanism and Treatment of Ischemia‐Reperfusion Injury DOI Creative Commons
Xinye Li, Ning Ma,

Juping Xu

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 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

Language: Английский

Citations

148