Nrf2 signaling pathway: Pivotal roles in inflammation

Ahmed, Syed Minhaj Uddin; Luo, Lin; Namani, Akhileshwar; Wang, Xiu Jun; Tang, Xiuwen

doi:10.1016/j.bbadis.2016.11.005

Cited by 1,368 publications

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“…During IRI, the damaged tissue produces excessive amounts of ROS, causing oxidative stress that results in mitochondrial oxidative phosphorylation, ATP depletion, increases in intracellular calcium, and activates membrane phospholipid proteases [37]. Nrf2 and Keap1 are two major proteins in the immune reaction that act as a complex in the cytoplasm to control intracellular oxidative stress [13, 38]. Tan et al found that upregulating Keap1 in hypomorphs protected mice against IRI, and was associated with a reduction in inflammatory gene expression and upregulation of Nrf2 target genes [39].…”

Section: Discussionmentioning

confidence: 99%

“…Kelch-like ECH-associated protein 1 (Keap1) binds Nrf2 in the cytoplasm, forming a complex that maintains Nrf2 at a low and steady level [12]. When IRI occurs, Keap1 undergoes conformational change and activates Nrf2, resulting in cellular protection against oxidative stress and enhancement of cell growth and survival [12, 13]. Hemeoxygenase-1 (HO-1) is one of the antioxidant response element (ARE)–dependent phase II detoxifying enzymes and antioxidants that are regulated by the redox-sensitive transcription factor Nrf2 [14-16].…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol Alleviates Inflammatory Responses and Oxidative Stress in Rat Kidney Ischemia-Reperfusion Injury and H2O2-Induced NRK-52E Cells via the Nrf2/TLR4/NF-κB Pathway

Wang

et al. 2018

Cell Physiol Biochem

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Background: Ischemia-reperfusion injury (IRI) is one of the major causes of postoperative renal allograft dysfunction, which is mainly the result of proinflammatory reactions including inflammatory responses, oxidative stress, and metabolic disorders. Resveratrol (RSV) plays an important role in protecting various organs in IRI because it reduces oxidative stress, lessens the inflammatory response, and exerts anti-apoptotic effects. The aim of this study was to demonstrate the renoprotective effect of RSV in inhibiting inflammatory responses, reducing oxidative stress, and decreasing cell apoptosis in vivo and in vitro. Methods: RSV was administered before renal ischemia and H₂O₂ induction. Serum and kidneys were harvested 24 h after reperfusion and NRK-52E cells were collected 4 h after H₂O₂ stimulation. Serum creatinine and blood urea nitrogen were used to assess renal function. Hematoxylin and eosin staining was performed to assess histological injury. Quantitative real-time PCR and enzyme-linked immunosorbent assay were used to assess proinflammatory cytokine expression. Oxidative stress–related proteins, such as Nrf2 and TLR4, were evaluated by western blot. Terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end labeling assay was used to detect apoptotic cells in tissues, and western blot was used to evaluate the expression of caspase-3, -8, and -9 in this study. Results: RSV inhibited inflammatory responses and improved renal function after renal IRI. Additionally, RSV decreased oxidative stress and reduced cell apoptosis by upregulating Nrf2 expression, downregulating the TLR4/NF-κB signaling pathway, and by decreasing caspase-3 activity and caspase cascades. Conclusion: Our study demonstrated the mechanisms underlying RSV renoprotection. We found that RSV exerts its greatest effects by blocking inflammatory responses, lowering oxidative stress, and reducing apoptosis via the Nrf2/TLR4/NF-κB pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Resveratrol Alleviates Inflammatory Responses and Oxidative Stress in Rat Kidney Ischemia-Reperfusion Injury and H2O2-Induced NRK-52E Cells via the Nrf2/TLR4/NF-κB Pathway

Wang

et al. 2018

Cell Physiol Biochem

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“…have been developed by cells to remove ROS and many of them are transcriptionally regulated by Nrf-2 (Nuclear factor erythroid 2-related factor 2), the master regulator of antioxidant response. Nrf2 is a transcription factor that in normal conditions is inhibited by Keap-1 (Kelch-like ECH-associated protein 1) that targets Nrf2 for ubiquitination and proteasomal degradation [12]. Under stress conditions, Nrf2 is stabilized and allows survival and stress adaptation upregulating the expression of some cytoprotective molecules, the antioxidant responses and the stress-mediated detoxification enzymes (NAD(P)H quinina reductase, glutathione S-transferase, superoxide dismutase, heme oxygenase, catalase and glutathione peroxidase) [13].…”

Section: Antioxidant Properties Of Mangifera Indica Lmentioning

confidence: 99%

Multifaceted Healthy Benefits of <em>Mangifera Indica</em> L. (Mango): The Inestimable Value of an Orchard Recently Rooted in Sicilian Rural Areas

Lauricella¹,

Emanuele²,

Calvaruso³

et al. 2017

Preprint

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Abstract:Historically, Mangifera indica L. cultivations have been widely rooted in tropical areas of India, Africa, Asia and Central America. However, at least 20 years ago its spreading allowed the development of some cultivars, also in Sicily, the South of Italy, where the favorable subtropical climate and adapted soils represent the perfect field to create new sources of production for Sicilian agricultural supply chain. Currently, cultivations of Kensington Pride, Keitt, Klenn, Maya and Tommy Atkins varieties are active in Sicilian island and their products meet the requirements of local and European markets. Mango plants produce fleshy stone fruits rich in phytochemicals with an undisputed nutritional value for its high content of flavonoids, vitamins, micro-and macro-elements, vital for maintaining health. This review provides an overview of the antioxidant, anti-inflammatory and anticancer properties of Mango, a fruit that should be included in everyone's diet for its multifaceted biochemical actions and nutraceutical potential.

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“…Na verdade, as vias de sinalização do Nrf2 e do NFκB interagem de forma complementar e especializada para a manutenção da homeostase celular. Contudo, devido à continuidade dos estímulos da inflamação crônica, a ativação do NFκB se sobressai, ocasionando morte celular, destruição tecidual e fibrose 23 . Tal processo pode ser observado em ilhotas pancreáticas de camundongos com inflamação crônica sistêmica desencadeada pela administração de lipopolissacarídeo, situação na qual ocorre ativação de vias inflamatórias dependentes de NFκB, aumento do dano oxidativo e de vias pró-apoptóticas e redução da translocação nuclear de Nrf2 24 .…”

Section: Relação Entre Nrf2 E Inflamaçãounclassified

O papel do fator nuclear eritroide 2 relacionado ao fator 2 (Nrf2) no diabetes mellitus

Hahn¹,

Oliveira²,

Bock³

2017

Clin. Biomed. Res.

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RESUMOO diabetes mellitus (DM) é uma doença metabólica complexa. Sua etiologia é atribuída a uma combinação entre fatores genéticos, ambientais e de estilo de vida. Contudo, sabe-se que o estresse oxidativo desempenha papel crucial na patogênese do DM, acarretando em disfunção das células β pancreáticas e resistência à insulina. Neste contexto, o fator nuclear eritroide 2 relacionado ao fator 2 (Nrf2) é considerado o regulador mestre da resposta antioxidante do organismo, sendo um mecanismo de importância crítica para a manutenção da homeostase e sobrevivência celular. Todavia, a função do Nrf2 não se limita somente à resposta antioxidante. Ao interagir com outras vias metabólicas, o Nrf2 possui importante papel na regulação do metabolismo, atuando no metabolismo dos lipídios, manutenção da glicemia, resposta inflamatória, entre outros. Entretanto, a exata relação do Nrf2 com outras vias metabólicas ainda não é totalmente conhecida. Contudo, sabe-se que o comprometimento da função do Nrf2 é evidente na fisiopatologia do DM bem como no desenvolvimento de suas complicações clínicas. A ativação do Nrf2 protege contra os danos mediados pelo DM, podendo ser adequada uma intervenção exógena para aumentar a sua atividade. Palavras-chave: Complicações do diabetes; estresse oxidativo; antioxidantes; inflamação; obesidade ABSTRACTDiabetes mellitus (DM) is a complex metabolic disease. Its etiology is attributed to a combination of genetic, environmental, and lifestyle factors. However, it is known that oxidative stress plays a crucial role in the pathogenesis of DM, leading to pancreatic β-cell dysfunction and insulin resistance. In this context, the nuclear factor-erythroid 2-related factor 2 (Nrf2) is considered the main regulator of the body's antioxidant response, being a mechanism of critical importance in the maintenance of homeostasis and cell survival. However, the role of Nrf2 is not limited to the antioxidant response alone. When interacting with other metabolic pathways, Nrf2 plays an important role in regulating metabolism, acting on lipid metabolism, in the maintenance of glycemia, and in inflammatory response, among others. However, the exact relationship of Nrf2 with other metabolic pathways is not yet fully understood. Nevertheless, impairment of Nrf2 function is known to be evident in the pathophysiology of DM as well as in the development of its clinical complications. Activation of the Nrf2 protects against damage mediated by DM, and an exogenous intervention may be adequate to increase its activity. Keywords: Diabetes complications; oxidative stress; antioxidants; inflammation; obesityO diabetes mellitus (DM) é uma doença metabólica crônica e progressiva que apresenta severas complicações. A sua principal característica clínica é a hiperglicemia crônica resultante de defeitos na secreção e/ou ação da insulina. De tal modo, a exposição crônica à hiperglicemia conduz a danos, disfunção e falência de diversos órgãos, afetando especialmente o coração, rins, olhos, nervos, ilhotas pancreáticas e vasos sanguí...

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Nrf2 signaling pathway: Pivotal roles in inflammation

Cited by 1,368 publications

References 149 publications

Resveratrol Alleviates Inflammatory Responses and Oxidative Stress in Rat Kidney Ischemia-Reperfusion Injury and H2O2-Induced NRK-52E Cells via the Nrf2/TLR4/NF-κB Pathway

Resveratrol Alleviates Inflammatory Responses and Oxidative Stress in Rat Kidney Ischemia-Reperfusion Injury and H2O2-Induced NRK-52E Cells via the Nrf2/TLR4/NF-κB Pathway

Multifaceted Healthy Benefits of <em>Mangifera Indica</em> L. (Mango): The Inestimable Value of an Orchard Recently Rooted in Sicilian Rural Areas

O papel do fator nuclear eritroide 2 relacionado ao fator 2 (Nrf2) no diabetes mellitus

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