International Journal of Molecular Sciences

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Osteoclasts are large, multinucleated cells that responsible for the resorption of bone.Bone degenerative diseases, such as osteoporosis, characterized by overactive osteoclasts.Receptor activator nuclear factor-κB (NF-κB) ligand (RANKL) binding to its receptor on osteoclast precursors will trigger formation and resorption.The production reactive oxygen species (ROS) is known play a crucial role in RANKL-induced resorption.G-protein coupled 120 (GPR120) signalling has been shown affect formation, but exact mechanisms action require further investigation.RAW264.7 murine macrophages were seeded into culture plates exposed GPR120 agonist, TUG-891, at varying concentrations (20-100 µM) RANKL induce formation.TUG-891 was inhibit without affecting cell viability RAW264.7 macrophages.TUG-891 decreased ROS when compared only cells.Antioxidant proteins, Nrf2, HO-1 NQO1 be upregulated while inducing protein, Nox1, downregulated TUG-891.Gene silencing revealed TUG-891 exerted effects specifically through GPR120.This study reveals may inhibition production.

Language: Английский

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The Roles of NRF2 in Modulating Cellular Iron Homeostasis

Antioxidants and Redox Signaling, Journal Year: 2017, Volume and Issue: 29(17), P. 1756 - 1773

Published: Aug. 10, 2017

Iron and oxygen are intimately linked: iron is an essential nutrient utilized as a cofactor in enzymes for transport, oxidative phosphorylation, metabolite oxidation. However, excess labile facilitates the formation of oxygen-derived free radicals capable damaging biomolecules. Therefore, biological utilization tightly regulated process. The nuclear factor (erythroid-derived 2)-like 2 (NRF2) transcription factor, which can respond to electrophilic stress, regulates several genes involved metabolism. Recent Advances: bulk NRF2 research has focused on its roles detoxification cancer prevention. works have identified that heme synthesis, hemoglobin catabolism, storage, export under control NRF2. Constitutive activation subsequent deregulation metabolism been implicated development: NRF2-mediated upregulation storage protein ferritin or oxygenase 1 lead enhanced proliferation therapy resistance. Of note, alterations signaling cancers may hinder efforts induce iron-dependent cell death process known ferroptosis.Despite growing recognition modulator signaling, exactly how altered due normal physiology pathologic conditions remains imprecise; moreover, changes disease progression only beginning be uncovered.Further studies necessary connect with physiological pathological stress. Antioxid. Redox Signal. 00, 000-000.

Language: Английский

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Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Jan. 3, 2019

The importance of gut microbiota in human health and pathophysiology is undisputable. Despite the abundance metagenomics data, functional dynamics disease remain elusive. Urolithin A (UroA), a major microbial metabolite derived from polyphenolics berries pomegranate fruits displays anti-inflammatory, anti-oxidative, anti-ageing activities. Here, we show that UroA its potent synthetic analogue (UAS03) significantly enhance barrier function inhibit unwarranted inflammation. We demonstrate UAS03 exert their functions through activation aryl hydrocarbon receptor (AhR)- nuclear factor erythroid 2-related 2 (Nrf2)-dependent pathways to upregulate epithelial tight junction proteins. Importantly, treatment with these compounds attenuated colitis pre-clinical models by remedying dysfunction addition anti-inflammatory Cumulatively, results highlight how metabolites provide two-pronged beneficial activities at epithelium enhancing reducing inflammation protect colonic diseases.

Language: Английский

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Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma

Journal of Clinical Investigation, Journal Year: 2018, Volume and Issue: 128(8), P. 3341 - 3355

Published: June 24, 2018

High-risk neuroblastoma is a devastating malignancy with very limited therapeutic options. Here, we identify withaferin A (WA) as natural ferroptosis-inducing agent in neuroblastoma, which acts through novel double-edged mechanism. WA dose-dependently either activates the nuclear factor–like 2 pathway targeting of Kelch-like ECH-associated protein 1 (noncanonical ferroptosis induction) or inactivates glutathione peroxidase 4 (canonical induction). Noncanonical induction characterized by an increase intracellular labile Fe(II) upon excessive activation heme oxygenase-1, sufficient to induce ferroptosis. This mechanism might explain superior efficacy compared etoposide cisplatin killing heterogeneous panel high-risk cells, and suppressing growth relapse rate xenografts. Nano-targeting allows systemic application suppressed tumor due enhanced accumulation at site. Collectively, our data propose strategy efficiently kill cancer cells

Language: Английский

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Activation of Nrf2/HO-1 signaling: An important molecular mechanism of herbal medicine in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress

Journal of Advanced Research, Journal Year: 2021, Volume and Issue: 34, P. 43 - 63

Published: July 6, 2021

Recently, Nrf2/HO-1 has received extensive attention as the main regulatory pathway of intracellular defense against oxidative stress and is considered an ideal target for alleviating endothelial cell (EC) injury.This paper aimed to summarized natural monomers/extracts that potentially exert protective effects in ECs.A literature search was carried out regarding our topic with keywords "atherosclerosis" or "Nrf2/HO-1" "vascular cells" "oxidative stress" "Herbal medicine" "natural products" extracts" compounds" "traditional Chinese medicines" based on classic books herbal medicine scientific databases including Pubmed, SciFinder, Scopus, Web Science, GoogleScholar, BaiduScholar, others. Then, we analyzed possible molecular mechanisms different types compounds treatment atherosclerosis via protection vascular cells from stress. In addition, perspectives future studies are discussed.These agents ECs mainly include phenylpropanoids, flavonoids, terpenoids, alkaloids. Most these alleviate apoptosis due stress, related signaling activation. However, despite continued progress research various aspects exerting EC injury by activating signaling, development new drugs (AS) other CVDs will require more detailed preclinical clinical studies.Our present provides updated information activities Nrf2/HO-1. We hope this review provide some directions further novel candidate AS CVDs.

Language: Английский

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Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

Antioxidants, Journal Year: 2019, Volume and Issue: 8(7), P. 235 - 235

Published: July 22, 2019

Poultry in commercial settings are exposed to a range of stressors. A growing body information clearly indicates that excess ROS/RNS production and oxidative stress major detrimental consequences the most common stressors poultry production. During evolution, antioxidant defence systems were developed survive an oxygenated atmosphere. They include complex network internally synthesised (e.g., enzymes, (glutathione) GSH, (coenzyme Q) CoQ) externally supplied (vitamin E, carotenoids, etc.) antioxidants. In fact, all antioxidants work cooperatively as team maintain optimal redox balance cell/body. This is key element providing necessary conditions for cell signalling, vital process regulation expression various genes, adaptation homeostasis maintenance body. Since considered be important signalling molecules, their concentration strictly regulated by conjunction with transcription factors vitagenes. activation vitagenes via such Nrf2 leads additional synthesis array protective molecules which can deal increased Therefore, it challenging task develop system supplementation help growing/productive birds effective defences On one hand, antioxidants, vitamin or minerals Se, Mn, Cu Zn) compulsory part pre-mixes poultry, and, cases, adequate meet physiological requirements these elements. other due aforementioned commercially relevant stressors, there need support poultry. new direction improving related opportunity activate (via Nrf2-related mechanisms: superoxide dismutase, SOD; heme oxygenase-1, HO-1; GSH thioredoxin, Heat shock protein (HSP)/heat factor (HSP), sirtuins, maximise internal AO protection maintenance. development vitagene-regulating nutritional supplements on agenda many companies worldwide.

Language: Английский

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Heme oxygenase-1 mediates BAY 11–7085 induced ferroptosis

Cancer Letters, Journal Year: 2017, Volume and Issue: 416, P. 124 - 137

Published: Dec. 20, 2017

Language: Английский

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A Dual Role of Heme Oxygenase-1 in Cancer Cells

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 20(1), P. 39 - 39

Published: Dec. 21, 2018

Heme oxygenase (HO)-1 is known to metabolize heme into biliverdin/bilirubin, carbon monoxide, and ferrous iron, it has been suggested demonstrate cytoprotective effects against various stress-related conditions. HO-1 commonly regarded as a survival molecule, exerting an important role in cancer progression its inhibition considered beneficial number of cancers. However, increasing studies have shown dark side HO-1, which acts critical mediator ferroptosis induction plays causative factor for the several diseases. Ferroptosis newly identified iron- lipid peroxidation-dependent cell death. The metabolism makes candidate mediate protective or detrimental via induction. This review summarizes current understanding on regulatory mechanisms ferroptosis. amount cellular iron reactive oxygen species (ROS) determinative momentum excessive ROS tend enforce from perpetrator. Despite that related death, there prospective application therapy chemotherapeutic strategy tumors.

Language: Английский

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Hesperetin, a Citrus Flavonoid, Attenuates LPS-Induced Neuroinflammation, Apoptosis and Memory Impairments by Modulating TLR4/NF-κB Signaling

Nutrients, Journal Year: 2019, Volume and Issue: 11(3), P. 648 - 648

Published: March 17, 2019

Glial activation and neuroinflammation play significant roles in apoptosis as well the development of cognitive memory deficits. Neuroinflammation is also a critical feature pathogenesis neurodegenerative disorders such Alzheimer Parkinson's diseases. Previously, hesperetin has been shown to be an effective antioxidant anti-inflammatory agent. In present study, vivo vitro analyses were performed evaluate neuroprotective effects lipopolysaccharide (LPS)-induced neuroinflammation, oxidative stress, neuronal impairments. Based on our findings, LPS treatment resulted microglial astrocytosis elevated expression inflammatory mediators phosphorylated-Nuclear factor-κB (p-NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) cortical hippocampal regions BV2 cells. However, cotreatment markedly reduced cytokines by ameliorating Toll-like receptor-4 (TLR4)-mediated ionized calcium-binding adapter molecule 1/glial fibrillary acidic protein (Iba-1/GFAP) expression. Similarly, attenuated LPS-induced generation reactive oxygen species/lipid per oxidation (ROS/LPO) improved level nuclear factor erythroid 2-related 2 (Nrf2) Haem-oxygenase (HO-1) mouse brain. Additionally, ameliorated cytotoxicity ROS/LPO induced HT-22 Moreover, rescued reducing phosphorylated-c-Jun N-terminal kinases (p-JNK), B-cell lymphoma (Bcl-2)-associated X (Bax), Caspase-3 promoting Bcl-2 level. Furthermore, enhanced synaptic integrity, cognition, processes enhancing phosphorylated-cAMP response element binding (p-CREB), postsynaptic density protein-95 (PSD-95), Syntaxin. Overall, preclinical study suggests that conferred neuroprotection regulating TLR4/NF-κB signaling pathway against detrimental LPS.

Language: Английский

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Nrf2 inhibits ferroptosis and protects against acute lung injury due to intestinal ischemia reperfusion via regulating SLC7A11 and HO-1

Aging, Journal Year: 2020, Volume and Issue: 12(13), P. 12943 - 12959

Published: June 29, 2020

Acute lung injury (ALI) is a syndrome associated with high mortality rate. Nrf2 key regulator of intracellular oxidation homeostasis that plays pivotal role in controlling lipid peroxidation, which closely related to the process ferroptosis. However, intrinsic effect on ferroptosis remains be investigated ALI. We found MDA expression increased while GSH and GPX4 decreased ALI models. Furthermore, characteristic mitochondrial morphological changes appear type II alveolar epithelial cells IIR Additional pre-treatment Fe Ferrostatin-1 significantly aggravated or ameliorated pathological injuries tissue, pulmonary edema, as well promoted prevented cell death, respectively. Knocking down notably SLC7A11 HO-1. Interference markedly Nrf2-HO-1 dramatically attenuated death OGD/R These findings indicate can inhibited by through regulating HO-1, may provide potential therapeutic strategy for IIR-ALI.

Language: Английский

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