The Keap1‐Nrf2 System: A Mediator between Oxidative Stress and Aging

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Oxidative stress, a term that describes the imbalance between oxidants and antioxidants, leads to disruption of redox signals causes molecular damage. Increased oxidative stress from diverse sources has been implicated in most senescence‐related diseases aging itself. The Kelch‐like ECH‐associated protein 1‐ (Keap1‐) nuclear factor‐erythroid 2‐related factor 2 (Nrf2) system can be used monitor stress; Keap1‐Nrf2 is closely associated with controls transcription multiple antioxidant enzymes. Simultaneously, signaling also modulated by more complex regulatory network, including phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt), C, mitogen‐activated kinase. This review presents information on aging‐related mechanisms involving Keap1‐Nrf2. Furthermore, we highlight several major involved Nrf2 unbinding Keap1, cysteine modification Keap1 phosphorylation Nrf2, PI3K/Akt/glycogen synthase 3 β , sequestosome 1, Bach1 c ‐ Myc . Additionally, discuss direct interaction mammalian target rapamycin pathway. In summary, focus recent progress research aging, providing an empirical basis for development antiaging drugs.

Language: Английский

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Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(5), P. 1223 - 1223

Published: March 11, 2019

Aging and various age-related diseases are associated with reductions in melatonin secretion, proinflammatory changes the immune system, a deteriorating circadian sirtuin-1 (SIRT1) activity. In non-tumor cells, several effects of abolished by inhibiting SIRT1, indicating mediation SIRT1. Melatonin is, addition to its antioxidant roles, an stimulatory agent. However, it can act as either pro- or anti-inflammatory regulator context-dependent way. stimulate release cytokines other mediators, but also, under different conditions, suppress inflammation-promoting processes such NO release, activation cyclooxygenase-2, inflammasome NLRP3, gasdermin D, toll-like receptor-4 mTOR signaling, cytokine SASP (senescence-associated secretory phenotype), amyloid-β toxicity. It also activates network, which SIRT1 activation, upregulation Nrf2 downregulation NF-κB, IL-4 IL-10 involved. A perhaps crucial action may be promotion macrophage microglia polarization favor phenotype M2. addition, many factors networks subject regulation microRNAs that target mRNAs respective upregulate them targeting their inhibitor proteins.

Language: Английский

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Resveratrol, Metabolic Syndrome, and Gut Microbiota

Nutrients, Journal Year: 2018, Volume and Issue: 10(11), P. 1651 - 1651

Published: Nov. 3, 2018

Resveratrol is a polyphenol which has been shown to have beneficial effects on metabolic syndrome-related alterations in experimental animals, including glucose and lipid homeostasis improvement reduction fat mass, blood pressure, low-grade inflammation, oxidative stress. Clinical trials carried out address its potential; however, results are still inconclusive. Even though resveratrol partly metabolized by gut microbiota, the relevance of this "forgotten organ" had not widely considered. However, past few years, data emerged suggesting that therapeutic potential compound may be due interaction with reporting changes bacterial composition associated outcomes. scarce for most part observational, it promising nevertheless, supplementation could useful tool treatment syndrome conditions.

Language: Английский

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Recent Advances of Natural Polyphenols Activators for Keap1‐Nrf2 Signaling Pathway

Chemistry & Biodiversity, Journal Year: 2019, Volume and Issue: 16(11)

Published: Sept. 4, 2019

Abstract The Keap1‐Nrf2/ARE signaling pathway is an important defense system against exogenous and endogenous oxidative stress injury. dysregulation of the associated with many diseases, such as cancer, diabetes, respiratory diseases. Over years, a wide range natural products has provided sufficient resources for discovery potential therapeutic drugs. Among them, polyphenols possess Nrf2 activation, not only inhibit production ROS, Keap1‐Nrf2 protein–protein interaction, but also degrade Keap1 regulate related pathway. In fact, continuous improvement separation purification technology further studies on molecular mechanism, more monomer components activators have been gradually discovered. this view, we summarize research status that found apparent activation their action modes. On whole, review may guide design novel activator.

Language: Английский

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Bioactive Compounds in Oxidative Stress-Mediated Diseases: Targeting the NRF2/ARE Signaling Pathway and Epigenetic Regulation

Antioxidants, Journal Year: 2021, Volume and Issue: 10(12), P. 1859 - 1859

Published: Nov. 23, 2021

Oxidative stress is a pathological condition occurring due to an imbalance between the oxidants and antioxidant defense systems in body. Nuclear factor E2-related 2 (NRF2), encoded by gene NFE2L2, master regulator of phase II enzymes that protect against oxidative inflammation. NRF2/ARE signaling has been considered as promising target stress-mediated diseases like diabetes, fibrosis, neurotoxicity, cancer. The consumption dietary phytochemicals acts effective modulator various acute chronic diseases. In present review, we discussed role NRF2 Alzheimer’s disease (AD), Parkinson’s (PD), cancer, atherosclerosis. Additionally, curcumin, quercetin, resveratrol, epigallocatechin gallate, apigenin, sulforaphane, ursolic acid have effectively modified prevented both vitro vivo models. Based on literature, it clear can prevent (1) blocking stress-inhibiting inflammatory mediators through inhibiting Keap1 or activating Nrf2 expression its downstream targets nucleus, including HO-1, SOD, CAT; (2) regulating kinases GSK3beta, PI3/AKT, MAPK; (3) modifying epigenetic modulation, such methylation, at promoter region; however, further investigation into other upstream molecules effect them still need be investigated near future.

Language: Английский

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Exosomes from adipose-derived stem cells alleviate the inflammation and oxidative stress via regulating Nrf2/HO-1 axis in macrophages

Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 165, P. 54 - 66

Published: Jan. 18, 2021

Language: Английский

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Stilbenes: Source plants, chemistry, biosynthesis, pharmacology, application and problems related to their clinical Application-A comprehensive review

Phytochemistry, Journal Year: 2022, Volume and Issue: 197, P. 113128 - 113128

Published: Feb. 17, 2022

Language: Английский

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Fructose and the Liver

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(13), P. 6969 - 6969

Published: June 28, 2021

Chronic diseases represent a major challenge in world health. Metabolic syndrome is constellation of disturbances affecting several organs, and it has been proposed to be liver-centered condition. Fructose overconsumption may result insulin resistance, oxidative stress, inflammation, elevated uric acid levels, increased blood pressure, triglyceride concentrations both the liver. Non-alcoholic fatty liver disease (NAFLD) term widely used describe excessive infiltration absence alcohol, autoimmune disorders, or viral hepatitis; attributed obesity, high sugar fat consumption, sedentarism. If untreated, NAFLD can progress nonalcoholic steatohepatitis (NASH), characterized by inflammation mild fibrosis addition and, eventually, advanced scar tissue deposition, cirrhosis, finally cancer, which constitutes culmination disease. Notably, fructose recognized as mediator NAFLD, significant correlation between intake degree found preclinical clinical studies. Moreover, risk factor for cancer development. Interestingly, induces number proinflammatory, fibrogenic, oncogenic signaling pathways that explain its deleterious effects body, especially

Language: Английский

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Remote ischemic conditioning attenuates oxidative stress and inflammation via the Nrf2/HO-1 pathway in MCAO mice

Redox Biology, Journal Year: 2023, Volume and Issue: 66, P. 102852 - 102852

Published: Aug. 17, 2023

The protective effects of remote ischemic conditioning (RIC) on acute stroke have been reported. However, the mechanisms RIC not fully elucidated. This study aimed to investigate whether could reduce oxidative stress and inflammatory responses in middle cerebral artery occlusion (MCAO)-reperfusion mice via nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. C57BL/6 were subjected MCAO underwent twice daily at 1, 3, 7 days after MCAO. ML385 was used specifically inhibit Nrf2 mice. Neurological deficit scores, infarct volume, hematoxylin-eosin (HE) staining assessed. Oxidative levels assessed based total antioxidant capacity (TAC), malonaldehyde (MDA), superoxide dismutase (SOD), glutathione/glutathione disulfide (GSH/GSSG). mRNA detected using real-time polymerase chain reaction (PCR), protein western blotting enzyme-linked immunosorbent assay (ELISA). Protein localization investigated immunofluorescence staining. significantly reduced volume improved neurological function histological changes increased TAC, SOD, GSH/GSSG decreased MDA levels. HO-1 Keap1, NLRP3, Cleaved Caspase-1 Nrf2, HO-1, NQO1 expression Caspase-1, IL-1β, IL-6, TNF-α expression. promoted activation translocation into nucleus. abolished by treatment. In conclusion, our findings suggest that alleviates Nrf2/HO-1 pathway, which turn improves neurobehavioral function. may provide novel therapeutic options for stroke.

Language: Английский

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Chronic Inflammation—A Link between Nonalcoholic Fatty Liver Disease (NAFLD) and Dysfunctional Adipose Tissue

Medicina, Journal Year: 2022, Volume and Issue: 58(5), P. 641 - 641

Published: May 6, 2022

Nonalcoholic fatty liver disease (NAFLD) is a new challenge in modern medicine, due to its high prevalence the world. The pathogenesis of NAFLD complex dysmetabolic process, following "multiple-hit" hypothesis that involves hepatocytes excessive accumulation triglycerides, insulin resistance (IR), increased oxidative stress, chronic low-grade inflammatory response and lipotoxicity. In this review, we provide an overview interrelation these processes, link between systemic local inflammation role dysfunctional adipose tissue (AT) development. Multiple extrahepatic triggers pathophysiological mechanisms are described: nutritional deficiency or malnutrition, unhealthy food intake, dysfunction liver-gut axis, involvement mesenteric tissue, adipokines such as adiponectin, intake hormone, leptin (LR) tissue's resistin. addition, wide range intrahepatic players involved: acid oxidation, endoplasmic reticulum mitochondrial dysfunction, resident macrophages (Kupffer cells), neutrophils, dendritic cells (DCs), B T lymphocytes contributing potential evolution nonalcoholic steatohepatitis (NASH). This interdependent approach imbalance NAFLD, integrating relevant studies, could contribute better clarification consequently development personalized treatments, targeting de novo lipogenesis, fibrosis. Further studies needed focus not only on treatment, but also prevention strategy NAFLD.

Language: Английский

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