Understanding the mechanistic roles of environmental heavy metal stressors in regulating ferroptosis: adding new paradigms to the links with diseases

APOPTOSIS, Год журнала: 2023, Номер 28(3-4), С. 277 - 292

Опубликована: Янв. 7, 2023

Язык: Английский

---

Inactivation of glutathione S -transferase alpha 4 blocks Enterococcus faecalis -induced bystander effect by promoting macrophage ferroptosis

Gut Microbes, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 16, 2025

Enterococcus faecalis-infected macrophages produce 4-hydroxynonenal (4-HNE) that mediates microbiota-induced bystander effect (MIBE) leading to colorectal cancer (CRC). Glutathione S-transferase alpha 4 (Gsta4), a specific detoxifying enzyme for 4-HNE, is overexpressed in human CRC and E. faecalis-induced murine CRC. However, the roles of Gsta4 colitis remain unclear. Herein, we demonstrate essential MIBE by protecting from ferroptosis. faecalis OG1RFSS was used induce Gsta4-/- Il10-/-/Gsta4-/- mice orogastric gavage. Ferroptosis assessed Gsta4-deficient macrophages. We found that, unlike Il10-/- mice, colonized with failed develop or Immunofluorescent staining showed reduction lamina propria faecalis-colonized as well decreased Gpx4 expression, indicating occurrence further confirmed infected faecalis. Moreover, inactivation induced upregulation Hmox1 phosphorylated c-Jun while blocked Nos2 accumulation intracellular ferrous iron, lipid peroxidation and, eventually, Finally, Mapk8, ferroptosis driver, remarkably elevated These results suggest blocks eliminating macrophages, thereby attenuates

Язык: Английский

---

Pancreatic acinar cell fate relies on system xC- to prevent ferroptosis during stress

Cell Death and Disease, Год журнала: 2023, Номер 14(8)

Опубликована: Авг. 21, 2023

Acinar cell dedifferentiation is one of the most notable features acute and chronic pancreatitis. It can also be initial step that facilitates pancreatic cancer development. In present study, we further decipher precise mechanisms regulation using primary human cells murine experimental models. Our RNAseq analysis indicates that, in both species, early acinar accompanied by multiple pathways related to survival are highly enriched, where SLC7A11 (xCT) transiently upregulated. xCT specific subunit cystine/glutamate antiporter system xC-. To its role, gene silencing, pharmacological inhibition a knock-out mouse model were used. with depleted or reduced function show an increase ferroptosis relating lipid peroxidation. Lower glutathione levels more ROS accumulation could rescued antioxidant N-acetylcysteine inhibitor ferrostatin-1. caerulein-induced pancreatitis mice, prevents peroxidation cells. conclusion, during stress, fate seems poised for avoiding several forms death. specifically fueling pool maintaining balance. The data suggest offers druggable tipping point steer stress conditions.

Язык: Английский

---

Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis

Science Advances, Год журнала: 2024, Номер 10(42)

Опубликована: Окт. 16, 2024

A major therapeutic barrier in melanoma is the coexistence of diverse cellular states marked by distinct metabolic traits. Transitioning from a proliferative to an invasive phenotype coupled with increased ferroptosis vulnerability. However, regulatory circuits controlling susceptibility across cell are unknown. In this work, we identified Apolipoprotein E ( APOE ) as top lipid-metabolism gene segregating MITF high /AXL low proliferative/ferroptosis-resistant invasive/ferroptosis-sensitive state. Mechanistically, ApoE secreted cells protects ferroptosis-inducing agents reducing content peroxidation-prone polyunsaturated fatty acids and boosting GPX4 levels both vitro vivo. Whole-exome sequencing indicates that expression patients associated resistance ferroptosis, regardless germline status. aggregate, found ferroptosis-resistance mechanism between relying on potential biomarker for poor response melanoma.

Язык: Английский

---

Acute pancreatitis: pathogenesis and emerging therapies

Journal of Pancreatology, Год журнала: 2023, Номер 7(1), С. 10 - 20

Опубликована: Дек. 29, 2023

Acute pancreatitis is a severe inflammatory disorder with limited treatment options. Improved understanding of disease mechanisms has led to new and potential therapies. Here we summarize what view as some the most promising therapies for treating acute pancreatitis, emphasizing rationale specific treatments based on mechanisms. Targeted pharmacologic interventions are highlighted. We explore benefits risks concerning reducing injury, minimizing complications, improving long-term outcomes. Mechanisms associated initiation, perpetuation, reconstitution highlighted, along therapeutic targets how these relate treatments.

Язык: Английский

---

Soat2 inhibitor avasimibe alleviates acute pancreatitis by suppressing acinar cell ferroptosis

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2024, Номер 397(8), С. 5989 - 5999

Опубликована: Фев. 20, 2024

Язык: Английский

---

Overexpression of Plakophilin2 Mitigates Capillary Leak Syndrome in Severe Acute Pancreatitis by Activating the p38/MAPK Signaling Pathway

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 4129 - 4149

Опубликована: Июнь 1, 2024

Purpose: Capillary leak syndrome (CLS) is an intermediary phase between severe acute pancreatitis (SAP) and multiple organ failure. As a result, CLS of clinical importance for enhancing the prognosis SAP. Plakophilin2 (PKP2), essential constituent desmosomes, plays critical role in promoting connections epithelial cells. However, function mechanism PKP2 SAP are not clear at present. Methods: We detected expression mice pancreatic tissue by transcriptome sequencing bioinformatics analysis. was overexpressed knocked down to assess its influence on cell permeability, cytoskeleton, tight junction molecules, adhesion associated pathways. Results: increased tissues human umbilical vein endothelial cells (HUVECs) after lipopolysaccharide (LPS) stimulation. overexpression only reduced permeability but also improved cytoskeleton relaxation response inflammatory levels ZO-1, occludin, claudin1, β-catenin, connexin43. The LPS-induced HUVECs counteracted inhibitory effect SB203580 (a p38/MAPK signaling pathway inhibitor) pathway, thereby restoring claudin1. Additionally, suppression eliminated enhanced claudin1 induced dehydrocorydaline. predicted that upstream transcription factor PPARγregulates expression, our findings demonstrate PPARγactivator rosiglitazone significantly upregulates PKP2, whereas antagonist GW9662 down-regulates PKP2. Administration increase stimulated LPS. Conversely, GW9662-induced reduction phosphorylated p38/p38, Conclusion: activation mitigates can up-regulate Overall, directing efforts toward could prove be feasible treatment approach effectively managing Keywords: pancreatitis, plakophilin2, capillary syndrome, junction,

Язык: Английский

---

Epithelial-mesenchymal Transition Promotes Metabolic Reprogramming to Suppress Ferroptosis

Seminars in Cancer Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

---

Carfilzomib promotes Iodine-125 seed radiation-induced apoptosis, paraptosis, and ferroptosis in esophageal squamous cell carcinoma by aggravating endoplasmic reticulum stress

Translational Oncology, Год журнала: 2025, Номер 57, С. 102393 - 102393

Опубликована: Май 1, 2025

Язык: Английский

---

Ferroptosis at the crossroads: Insights and advances in non-neoplastic pancreatic diseases

International Immunopharmacology, Год журнала: 2025, Номер 158, С. 114870 - 114870

Опубликована: Май 17, 2025

Ferroptosis is a form of regulated cell death characterized by iron accumulation and increased lipid peroxidation, primarily counteracted range antioxidant molecules, including glutathione (GSH), peroxidase 4 (GPX4), ubiquinone, tetrahydrofolate, nuclear respiratory factor 2. Furthermore, the process ferroptosis intricately influenced opposing actions p53 tumor suppressor gene activated transcription factors 3 4, which can either facilitate or hinder ferroptotic depending on cellular context. This significantly associated with various pancreatic disorders, both acute chronic pancreatitis, as well diabetes mellitus. In this review, we thoroughly investigate mechanisms underlying ferroptosis, focusing overload, regulatory molecules involved in modulation (notably system xc-/GSH/GPX4 axis), along relevant signaling pathways. We also examine role non-neoplastic diseases such pancreatitis mellitus while identifying novel therapeutic agents that target potentially paving way for innovative treatment strategies conditions.

Язык: Английский

---