International Immunopharmacology, Journal Year: 2023, Volume and Issue: 122, P. 110566 - 110566
Published: July 6, 2023
Language: Английский
Autophagy, Journal Year: 2023, Volume and Issue: 19(10), P. 2621 - 2638
Published: June 4, 2023
Selenoprotein GPX4 (glutathione peroxidase 4), originally known as PHGPX (phospholipid hydroperoxide glutathione peroxidase), is the main oxidoreductase in use of a reducing agent scavenging lipid peroxidation products. There are three isoforms: cytosolic (cGPX4), mitochondrial (mGPX4), and nuclear (nGPX4), with distinct spatiotemporal expression patterns during embryonic development adult life. In addition to inducing phenotype ferroptosis, loss can some cells trigger apoptosis, necroptosis, pyroptosis, or parthanatos, which mediates accelerates developmental defects, tissue damage, sterile inflammation. The interaction autophagic degradation pathway further modulates cell fate response oxidative stress. Impaired function implicated tumorigenesis, neurodegeneration, infertility, inflammation, immune disorders, ischemia-reperfusion injury. Additionally, R152H mutation promote Sedaghatian-type spinal metaphyseal dysplasia, rare fatal disease newborns. Here, we discuss roles classical functions well emerging GPX4-regulated processes death, autophagy, disease.Abbreviations: AA: arachidonic acid; cGPX4: GPX4; CMA: chaperone-mediated autophagy; DAMPs: danger/damage-associated molecular patterns; mGPX4: nGPX4: GSDMD-N: N-terminal fragment GSDMD; I/R: ischemia-reperfusion; PLOOH: phospholipid hydroperoxide; PUFAs: polyunsaturated fatty acids; RCD: regulated death; ROS: reactive oxygen species; Se: selenium; SSMD: spondylometaphyseal dysplasia; UPS: ubiquitin-proteasome system
Language: Английский
Citations
230
Bone Research, Journal Year: 2022, Volume and Issue: 10(1)
Published: Sept. 20, 2022
Abstract Osteoarthritis (OA) is the most common degenerative joint disease that causes painful swelling and permanent damage to joints in body. The molecular mechanisms of OA are currently unknown. a heterogeneous affects entire joint, multiple tissues altered during development. To better understand pathological OA, new approaches, methods, techniques need be used pathogenesis. In this review, we first focus on epigenetic regulation with particular DNA methylation, histone modification, microRNA regulation, followed by summary several key mediators OA-associated pain. We then introduce innovative have been will continue fields pain, such as CRISPR, scRNA sequencing, lineage tracing. Next, discuss timely updates concerning cell death pathology, including pyroptosis, ferroptosis, autophagy, well their individual roles potential targets treating OA. Finally, our review highlights directions role synovial lymphatic system An improved understanding pathogenesis aid development more specific effective therapeutic interventions for
Language: Английский
Citations
224
Trends in Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(9), P. 753 - 764
Published: June 24, 2023
Ferroptosis suppressor protein 1 (FSP1) is one of the main regulatory molecules ferroptosis. FSP1 functions through FSP1-coenzyme Q10 (CoQ10)-NAD(P)H axis and vitamin K redox cycle. regulated by upstream factors, including transcription factors noncoding RNA (ncRNA), subject to epigenetic modifications, which affect progress FSP1-related diseases. closely associated with poor prognosis malignant tumors plays an important role in disease treatment. This review aims provide a comprehensive understanding ferroptosis regulation summarizing pathways, possible mechanisms involving FSP1, relationship between
Language: Английский
Citations
106
Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)
Published: Aug. 29, 2023
Abstract Osteoarthritis (OA) is a multifactorial and increasingly prevalent degenerative disease that affects the whole joint. The pathogenesis of OA poorly understood there lack therapeutic interventions to reverse pathological process this disease. Accumulating studies have shown overproduction reactive oxygen species (ROS) ROS-induced lipid peroxidation are involved in OA. 4-Hydroxy-2-nonenal (4-HNE) malondialdehyde (MDA) received considerable attention for their role cartilage degeneration subchondral bone remodeling during development. Ferroptosis form cell death characterized by control membrane recent suggested chondrocyte ferroptosis contributes progression. In review, we aim discuss peroxidation-derived 4-HNE MDA progression addition, potential controlling accumulation inhibiting discussed.
Language: Английский
Citations
69
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: Oct. 14, 2024
Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against
Language: Английский
Citations
56
Food and Chemical Toxicology, Journal Year: 2023, Volume and Issue: 174, P. 113644 - 113644
Published: Jan. 30, 2023
Language: Английский
Citations
55
Bone Research, Journal Year: 2024, Volume and Issue: 12(1)
Published: Feb. 23, 2024
Abstract Piezo proteins are mechanically activated ion channels, which required for mechanosensing functions in a variety of cell types. While we and others have previously demonstrated that the expression Piezo1 osteoblast lineage cells is essential bone-anabolic processes, there was only suggestive evidence indicating role and/or Piezo2 cartilage. Here addressed question if how chondrocyte mechanosensitive or controls physiological endochondral ossification pathological osteoarthritis (OA) development. Mice with chondrocyte-specific inactivation ( Col2a1Cre ), but not Piezo2, developed near absence trabecular bone below chondrogenic growth plate postnatally. Moreover, all animals displayed multiple fractures rib bones at 7 days age, were located close to plates. skeletal mildly affected these mice, OA pathologies markedly less pronounced compared littermate 60 weeks age. Likewise, when induced by anterior cruciate ligament transection, Piezo1, resulted attenuated articular cartilage degeneration. Importantly, osteophyte formation maturation also reduced mice. We further observed increased protein abundance cartilaginous zones human osteophytes. Finally, identified Ptgs2 Ccn2 as potentially relevant downstream genes chondrocytes. Collectively, our data do demonstrate critical regulator suggest antagonists may be established novel approach limit OA.
Language: Английский
Citations
31
Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)
Published: Jan. 22, 2024
Abstract Intervertebral disc degeneration (IVDD) is one of the most prevalent spinal degenerative disorders and imposes places heavy medical economic burdens on individuals society. Mechanical overloading applied to intervertebral (IVD) has been widely recognized as an important cause IVDD. overloading-induced chondrocyte ferroptosis was reported, but potential association between mechanical remains be illustrated in nucleus pulposus (NP) cells. In this study, we discovered that excessive loading induced endoplasmic reticulum (ER) stress, which were detected by mitochondria associated markers, increasing intracellular free Ca 2+ level through Piezo1 ion channel localized plasma membrane ER NP Besides, proposed elevation activation stress are positive feedback processes promote each other, consistent with results coccygeal discs aged Piezo1-CKO mice significantly lower than WT mice. Then, confirmed selenium supplementation decreased mitigating upregulating Selenoprotein K (SelK) expression. caused impaired production function Glutathione peroxidase 4 (GPX4) due calcium overload could improved Se-GPX4 axis Se-SelK vivo vitro, eventually presenting stabilization extracellular matrix (ECM). Our findings reveal role IVDD, promotes significance attenuate thus alleviates might provide insights into therapeutic interventions for
Language: Английский
Citations
23
Bone Research, Journal Year: 2024, Volume and Issue: 12(1)
Published: March 29, 2024
Abstract To date, several molecules have been found to facilitate iron influx, while the types of influx channels remain be elucidated. Here, Piezo1 channel was identified as a key transporter in response mechanical stress. Piezo1-mediated overload disturbed metabolism and exaggerated ferroptosis nucleus pulposus cells (NPCs). Importantly, Piezo1-induced independent transferrin receptor (TFRC), well-recognized gatekeeper. Furthermore, pharmacological inactivation profoundly reduced accumulation, alleviated mitochondrial ROS, suppressed ferroptotic alterations stimulation Moreover, conditional knockout ( Col2a1-CreERT flox/flox ) attenuated injury-induced intervertebral disc degeneration (IVDD). Notably, protective effect deficiency IVDD dampened Piezo1/Gpx4 double (cDKO) mice /Gpx4 ). These findings suggest that is potential determinant indicating Piezo1-iron-ferroptosis axis might shed light on treatment stress-induced diseases.
Language: Английский
Citations
20
Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
The aim of this study was to investigate the potential molecular mechanisms by which taurine protects against cartilage degeneration. anterior cruciate ligament transection (ACLT) surgery used construct an animal model osteoarthritis (OA). Metabolomics identify characteristic metabolites in osteoarthritic chondrocytes. Transcriptomics and metabolomics were explore small molecule metabolite inflammatory chondrocyte damage. Cell transfection inhibitors/agonists validate chondrocytes vitro. Finally, adeno-associated virus degeneration vivo. Metabolomic assays identified as a possible key metabolic progression OA. revealed that O-GlcNAc transferase (OGT)-dependent O-GlcNAcylation Gpx4-dependent ferroptosis may mediate protective effects on chondrocytes, further confirmed gain loss function Subsequently, experiments indicated existence direct binding site for Gpx4 OGT proteins, provides evidence presence modification protein. Finnaly, we demonstrated OGT-dependent be Antioxidant inhibits through upregulation OGT/Gpx4 signaling. Supplementation with taurine, safe nonessential amino acid, therapeutic strategy
Language: Английский
Citations
2