Kaempferol Ameliorates Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Ferroptosis by Activating Nrf2/SLC7A11/GPX4 Axis

Biomolecules, Год журнала: 2021, Номер 11(7), С. 923 - 923

Опубликована: Июнь 22, 2021

Kaempferol has been shown to protect cells against cerebral ischemia/reperfusion injury through inhibition of apoptosis. In the present study, we sought investigate whether ferroptosis is involved in oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal and effects kaempferol on OGD/R-treated neurons. Western blot, immunofluorescence, transmission electron microscopy were used analyze ferroptosis, whereas cell death was detected using lactate dehydrogenase (LDH) release. We found that OGD/R attenuated SLC7A11 glutathione peroxidase 4 (GPX4) levels as well decreased endogenous antioxidants including nicotinamide adenine dinucleotide phosphate (NADPH), (GSH), superoxide dismutase (SOD) Notably, enhanced accumulation lipid peroxidation, leading induction However, activated nuclear factor-E2-related factor 2 (Nrf2)/SLC7A11/GPX4 signaling, augmented antioxidant capacity, suppressed peroxidation Furthermore, significantly reversed OGD/R-induced ferroptosis. Nevertheless, Nrf2 by ML385 blocked protective These results suggest may be a significant cause associated with OGD/R. provides protection from partly activating Nrf2/SLC7A11/GPX4 signaling pathway.

Язык: Английский

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Fighting age-related orthopedic diseases: focusing on ferroptosis

Bone Research, Год журнала: 2023, Номер 11(1)

Опубликована: Март 1, 2023

Abstract Ferroptosis, a unique type of cell death, is characterized by iron-dependent accumulation and lipid peroxidation. It closely related to multiple biological processes, including iron metabolism, polyunsaturated fatty acid the biosynthesis compounds with antioxidant activities, glutathione. In past 10 years, increasing evidence has indicated potentially strong relationship between ferroptosis onset progression age-related orthopedic diseases, such as osteoporosis osteoarthritis. Therefore, in-depth knowledge regulatory mechanisms in diseases may help improve disease treatment prevention. This review provides an overview recent research on its influences bone cartilage homeostasis. begins brief systemic metabolism ferroptosis, particularly potential ferroptosis. presents discussion role promotion loss degradation inhibition osteogenesis. Finally, it focuses future targeting treat intention inspiring further clinical development therapeutic strategies.

Язык: Английский

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Oxidative stress in intervertebral disc degeneration: Molecular mechanisms, pathogenesis and treatment

Cell Proliferation, Год журнала: 2023, Номер 56(9)

Опубликована: Март 13, 2023

Abstract Low back pain (LBP) is a leading cause of labour loss and disability worldwide, it also imposes severe economic burden on patients society. Among symptomatic LBP, approximately 40% caused by intervertebral disc degeneration (IDD). IDD the pathological basis many spinal degenerative diseases such as herniation stenosis. Currently, therapeutic approaches for mainly include conservative treatment surgical treatment, neither which can solve problem from root terminating process (IVD). Therefore, further exploring pathogenic mechanisms adopting targeted strategies one current research hotspots. complex pathophysiological processes IDD, oxidative stress considered main factor. The delicate balance between reactive oxygen species (ROS) antioxidants essential maintaining normal function survival IVD cells. Excessive ROS levels damage to macromolecules nucleic acids, lipids, proteins cells, affect cellular activities functions, ultimately lead cell senescence or death. This review discusses potential role in understand provides IDD.

Язык: Английский

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Polydopamine Nanoparticles Targeting Ferroptosis Mitigate Intervertebral Disc Degeneration Via Reactive Oxygen Species Depletion, Iron Ions Chelation, and GPX4 Ubiquitination Suppression

Advanced Science, Год журнала: 2023, Номер 10(13)

Опубликована: Март 23, 2023

Intervertebral disc degeneration (IVDD)-induced lower back pain (LBP) is a common problem worldwide. The underlying mechanism partially accredited to ferroptosis, based on sequencing analyses of IVDD patients from the gene expression omnibus (GEO) databases. In this study, it shown that polydopamine nanoparticles (PDA NPs) inhibit oxidative stress-induced ferroptosis in nucleus pulposus (NP) cells vitro. PDA NPs scavenge reactive oxygen species (ROS), chelate Fe

Язык: Английский

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Ferroptosis in sepsis: The mechanism, the role and the therapeutic potential

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Авг. 5, 2022

Sepsis is a common critical illness in the Intensive care unit(ICU) and its management treatment has always been major challenge medicine. The dysregulated host response to infection, causing systemic multi-organ multi-system damage main pathogenesis. Notably, intense stress during sepsis can lead metabolic disturbances of ions, lipids energy organism. Ferroptosis an iron-dependent, non-apoptotic cell death distinguished by disruption iron metabolism iron-dependent accumulation lipid peroxides. Mounting researches have established that ferroptosis essential part anti-inflammatory sepsis, drugs targeting ferroptosis-related molecules, such as inhibitors, are gradually proving their effectiveness sepsis. This paper summarizes reviews pathogenesis ferroptosis, regulatory network, vital involvement initiation related organ damage, finally discusses possible target provided above mechanisms, describes dilemmas well outlook, hope finding more links between providing new perspectives for future

Язык: Английский

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Endometrial stromal cell ferroptosis promotes angiogenesis in endometriosis

Cell Death Discovery, Год журнала: 2022, Номер 8(1)

Опубликована: Янв. 17, 2022

Endometriosis, a chronic disorder characterised by the presence of endometrial-like tissue outside uterus, is associated with iron overload and oxidative stress in lesion. Although it well established that can trigger ferroptosis, results previous studies on ferroptosis resistance endometriotic lesions are paradoxical. Here, we found some stromal cells cyst walls were contact fluid underwent ferroptosis. Surprisingly, endometrial cell triggered production angiogenic, inflammatory growth cytokines. In particular, angiogenic cytokines, such as vascular endothelial factor A (VEGFA) interleukin 8 (IL8), promoted human umbilical vein (HUVEC) formation vitro. Moreover, inhibition p38 mitogen-activated protein kinase/signal transducer activator transcription 6 (p38 MAPK/STAT6) signalling represses VEGFA IL8 expression when undergo Notably, showed localised significantly upregulated ectopic compared to control eutopic endometrium samples from patients endometriosis. Thus, our study reveals ovarian endometrioma may cytokine secretion promote angiogenesis adjacent via paracrine actions drive development endometriosis, providing rationale for translation into clinical practice developing drugs

Язык: Английский

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The deubiquitinase USP11 ameliorates intervertebral disc degeneration by regulating oxidative stress-induced ferroptosis via deubiquitinating and stabilizing Sirt3

Redox Biology, Год журнала: 2023, Номер 62, С. 102707 - 102707

Опубликована: Апрель 20, 2023

Increasing studies have reported that intervertebral disc degeneration (IVDD) is the main contributor and independent risk factor for low back pain (LBP), it would be, therefore, enlightening investigating exact pathogenesis of IVDD developing target-specific molecular drugs in future. Ferroptosis a new form programmed cell death characterized by glutathione (GSH) depletion, inactivation regulatory core antioxidant system (glutathione system) GPX4. The close relationship oxidative stress ferroptosis has been studied various diseases, but crosstalk between not explored IVDD. At beginning current study, we proved Sirt3 decreases occurs after Next, found knockout (Sirt3-/-) promoted poor pain-related behavioral scores via increasing stress-induced ferroptosis. (immunoprecipitation coupled with mass spectrometry) IP/MS co-IP demonstrated USP11 was identified to stabilize directly binding deubiquitinating Sirt3. Overexpression significantly ameliorate ferroptosis, thus relieving Moreover, vivo (USP11-/-) resulted exacerbated scores, which could be reversed overexpression disc. In conclusion, study emphasized importance interaction pathological process regulating USP11-mediated as promising target treating

Язык: Английский

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International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis

Autophagy, Год журнала: 2024, Номер 20(6), С. 1213 - 1246

Опубликована: Март 6, 2024

Macroautophagy/autophagy is a complex degradation process with dual role in cell death that influenced by the types are involved and stressors they exposed to. Ferroptosis an iron-dependent oxidative form of characterized unrestricted lipid peroxidation context heterogeneous plastic mechanisms. Recent studies have shed light on involvement specific autophagy (e.g. ferritinophagy, lipophagy, clockophagy) initiating or executing ferroptotic through selective anti-injury proteins organelles. Conversely, other forms reticulophagy lysophagy) enhance cellular defense against damage. Dysregulated autophagy-dependent ferroptosis has implications for diverse range pathological conditions. This review aims to present updated definition ferroptosis, discuss influential substrates receptors, outline experimental methods, propose guidelines interpreting results.

Язык: Английский

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Selenium-SelK-GPX4 axis protects nucleus pulposus cells against mechanical overloading-induced ferroptosis and attenuates senescence of intervertebral disc

Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)

Опубликована: Янв. 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

Язык: Английский

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Mechanisms of Ferroptosis in bone disease: A new target for osteoporosis treatment

Cellular Signalling, Год журнала: 2025, Номер 127, С. 111598 - 111598

Опубликована: Янв. 7, 2025

Язык: Английский

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