Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 17, 2025

Drug resistance is a common challenge in clinical tumor treatment. A reduction drug sensitivity of cells often accompanied by an increase autophagy levels, leading to autophagy-related resistance. The effectiveness combining chemotherapy drugs with inducers/inhibitors has been widely confirmed, but the mechanisms are still unclear. Ferroptosis and pyroptosis can be affected various types autophagy. Therefore, ferroptosis have crosstalk via autophagy, potentially switch cell death under certain conditions. As two forms inflammatory programmed death, different effects on inflammation, cGAS-STING signaling pathway also involved. it plays important role progression some chronic diseases. This review discusses relationship between pyroptosis, attempts uncover reasons behind evasion nature

Language: Английский

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Hypoxia‐Inducible Factor‐1α Regulates BNIP3‐Dependent Mitophagy and Mediates Metabolic Reprogramming Through Histone Lysine Lactylation Modification to Affect Glioma Proliferation and Invasion

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(2)

Published: Jan. 20, 2025

ABSTRACT Objective Gliomas are the predominant form of malignant brain tumors. We investigated mechanism hypoxia‐inducible factor‐1α (HIF‐1α) affecting glioma metabolic reprogramming, proliferation and invasion. Methods Human cell U87 was cultured under hypoxia treated with small interfering (si)HIF‐1α, si‐B lymphoma‐2/adenovirus E1B 19‐kDa interacting protein 3 (siBNIP3), si‐YT521‐B homology domain 2 (siYTHDF2), 3‐methyladenine 2‐deoxyglucose, exogenous sodium lactate‐treated normally‐cultured cells as a lactate‐positive control. Cellular hexokinase 2, lactate dehydrogenase A pyruvate kinase 1 enzyme activities, glucose uptake, levels lactic acid adenosine triphosphate (ATP), HIF‐1α, glycolysis‐related proteins, mitophagy‐related histone H3 lysine 18 lactylation (H3K18la) YTHDF2 were determined by ELISA, 2‐NBDG, kits, Western blot. Extracellular acidification rate (ECAR), proliferation, invasion, apoptosis mitophagy evaluated extracellular flux analysis, CCK‐8, Transwell, flow cytometry, immunofluorescence staining. H3K18la‐YTHDF2 relationship YTHDF2‐BNIP3 interaction assessed ChIP Co‐IP assays. Results Hypoxia‐induced highly‐expressed HIF‐1α in increased levels, glycolytic production, ATP level ECAR, thereby promoting invasion proliferation. mediated through BNIP3‐dependent mitophagy, which partly negated inhibition. induced Kla modification to upregulate YTHDF2. downregulation impeded inhibited HIF‐1α‐induced curbing Conclusions high expression upregulated hH3K18la modification, enhanced interaction, regulated mitophagy‐mediated reprogramming affect

Language: Английский

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Study on the Effect of Deer Bone in Improving Rheumatoid Arthritis Based on the “Drug-Target-Pathway” Association Network

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119684 - 119684

Published: March 1, 2025

Language: Английский

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BNIP3-mediated mitophagy aggravates placental injury in preeclampsia via NLRP1 inflammasome

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

Published: April 2, 2025

Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by pronounced placental oxidative stress and inflammatory damage. However, the contribution mitophagy to inflammation-induced injury in PE remains unclear. Human placenta samples were collected from 15 normal pregnant women preeclampsia women. Protein expression was analyzed western blotting, while immunofluorescence staining employed localize mediators. Mitochondrial reactive oxygen species quantified using MitoSOX. The concentrations pro-inflammatory cytokines ELISA, ultrastructural alterations evaluated transmission electron microscopy. To investigate molecular mechanisms vivo, mouse model established via daily subcutaneous administration L-NAME, followed tail vein delivery AAV9 carrying shRNA for targeted gene knockdown. In this study, we demonstrate that BNIP3-mediated NLRP1 inflammasome activation occur an L-NAME-induced human placenta. results also indicate knockdown BNIP3 abolishes JEG3 cells H/R condition, suggesting positive regulatory role controlling NLRP1-dependent inflammation. Furthermore, silencing leads significant reduction mitochondrial damage mtROS production. Treatment with MitoTEMPO after further decreases NLRP1, overexpression nullifies impact Additionally, alleviates model. These findings reveal novel mechanism through which exacerbates H/R-induced inducing production activating PE.

Language: Английский

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Mitochondrial dysfunction induced by HIF‐1α under hypoxia contributes to the development of gastric mucosal lesions

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(4)

Published: April 1, 2024

Abstract Introduction Hypoxia is an important characteristic of gastric mucosal diseases, and hypoxia‐inducible factor‐1α (HIF‐1α) contributes to microenvironment disturbance metabolic spectrum abnormalities. However, the underlying mechanism HIF‐1α its association with mitochondrial dysfunction in lesions under hypoxia have not been fully clarified. Objectives To evaluate effects hypoxia‐induced on development lesions. Methods Portal hypertensive gastropathy (PHG) cancer (GC) were selected as representative diseases benign malignant lesions, respectively. Gastric tissues from patients diagnosed above collected. hypertension (PHT)‐induced mouse models METTL3 mutant or NLRP3 ‐deficient littermates established, nude graft tumour relevant inhibitors generated. The mechanisms hypoxic condition, alterations further analysed. Results HIF‐1α, which can mediate via upregulation METTL3/IGF2BP3‐dependent dynamin‐related protein 1 (Drp1) N6‐methyladenosine modification increase reactive oxygen species (mtROS) production, was elevated conditions human portal mucosa GC tissues. While blocking PX‐478, inhibiting Drp1‐dependent fission division inhibitor (Mdivi‐1) treatment mutation alleviated this process. Furthermore, influenced energy metabolism by enhancing glycolysis lactate dehydrogenase A. In addition, HIF‐1α‐induced also enhanced glycolysis. associated antioxidant enzyme activity electron transport chain, resulting massive mtROS needed for activation inflammasome aggravate PHG GC. Conclusions Under conditions, enhances influences profile altering trigger contribute

Language: Английский

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Mitophagy-associated programmed neuronal death and neuroinflammation

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

Published: Oct. 2, 2024

Mitochondria are crucial organelles that play a central role in cellular metabolism and programmed cell death eukaryotic cells. Mitochondrial autophagy (mitophagy) is selective process where damaged mitochondria encapsulated degraded through autophagic mechanisms, ensuring the maintenance of both mitochondrial homeostasis. Excessive neurons can result functional impairments following cerebral ischemia trauma, as well chronic neurodegenerative diseases, leading to irreversible declines motor cognitive functions. Neuroinflammation, an inflammatory response nervous system factors disrupting homeostasis, common feature across various neurological events, including ischemic, infectious, traumatic, conditions. Emerging research suggests regulating may offer promising therapeutic avenue for treating certain diseases. Furthermore, existing literature indicates small molecule regulators have been tested animal models linked disease outcomes. This review explores mitophagy neuronal its connection neuroinflammation.

Language: Английский

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IRF1-mediated upregulation of PARP12 promotes cartilage degradation by inhibiting PINK1/Parkin dependent mitophagy through ISG15 attenuating ubiquitylation and SUMOylation of MFN1/2

Bone Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Oct. 28, 2024

Abstract Osteoarthritis (OA) is an age-related cartilage-degenerating joint disease. Mitochondrial dysfunction has been reported to promote the development of OA. Poly (ADP-ribose) polymerase family member 12 (PARP12) a key regulator mitochondrial function, protein translation, and inflammation. However, role PARP12 in OA-based cartilage degradation underlying mechanisms are relatively unknown. Here, we first demonstrated that inhibits mitophagy promotes OA progression human monosodium iodoacetate-induced rat model. Using mass spectrometry co-immunoprecipitation assay, was shown interact with ISG15, upregulate mitofusin 1 2 (MFN1/2) ISGylation, which downregulated MFN1/2 ubiquitination SUMOylation, thereby inhibiting PINK1/Parkin-dependent chondrocyte promoting degradation. Moreover, inflammatory cytokine-induced interferon regulatory factor (IRF1) activation required for upregulation expression, it directly bound promoter activate transcription. XAV-939 inhibited expression suppressed pathogenesis vitro vivo. Clinically, can be used predict severity OA; thus, represents new target study progression. In brief, IRF1-mediated promoted by via ISG15-based attenuation ubiquitylation SUMOylation. Our data provide insights into molecular PARP12-based regulation facilitate therapeutic strategies treatment

Language: Английский

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Identification of stable reference genes for quantitative real-time PCR in human fibroblasts from lymph nodes and synovium

Published: July 12, 2024

Abstract Real-time quantitative PCR (RT–qPCR) has emerged as an accurate and widely used technique for measuring gene expression levels. However, its reliability depends on the selection of appropriate reference genes to normalize sample input. Accordingly, identification characterized by stable in cells conditions interest is essential ensuring values. To date, no study specifically identified suitable primary human cultured fibroblast-like synoviocytes (FLS) lymph node stromal (LNSCs) within context rheumatoid arthritis (RA). These play a critical role pathogenesis disease. In this study, we evaluated suitability 15 candidate normalizing transcript FLS LNSCs subjected various vitro stimuli. We included traditional often normalization fibroblasts well via GeneVestigator analysis publicly available transcriptomic data. RefFinder algorithms were identify most across cell types different experimental conditions. determined that optimal number every condition tested was two; RPLP0 POLR2G exhibited greatest stability LNSCs. FLS, observed greater variability Although TBP under unstimulated conditions, our findings indicated require distinct depending specific Validation selected levels metabolic emphasized importance prior evaluation potential genes, arbitrary could lead data misinterpretation. This constitutes first systematic selecting fibroblasts. Our emphasize proper each separately when applying standard technology assessing

Language: Английский

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Research Progress of Traditional Chinese Medicine in Regulating Macrophage Polarization, Pyroptosis and Glucose Metabolism in Rheumatoid Arthritis

Advances in Clinical Medicine, Journal Year: 2024, Volume and Issue: 14(10), P. 746 - 753

Published: Jan. 1, 2024

Language: Английский

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FOXO3 as a potential diagnostic biomarker for autophagy in rheumatoid arthritis: A bioinformatics study

Autoimmunity, Journal Year: 2024, Volume and Issue: 57(1)

Published: Nov. 5, 2024

This study aimed to identify genes associated with autophagy and potential diagnostic biomarkers by comparing the gene expression profiles of synovial tissues in patients rheumatoid arthritis (RA) healthy individuals, aiming offer new insights for clinical treatment strategies. We used publicly available datasets analyze differentially expressed (DEGs) between tissue RA individuals. Then, we intersected these DEGs autophagy-related patients. further analyzed biological processes functions genes. Furthermore, machine learning characteristic tissue. Finally, examined differential blood using an external dataset. Our identified FOXO3 as a biomarker diagnosing RA. was downregulated both patients, suggesting its involvement multiple such local inflammation, oxidative stress, metabolic processes, immune responses. findings suggest that may be novel diagnosis play crucial role pathogenesis The provides into molecular mechanisms therapeutic targets.

Language: Английский

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