Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways

Wardyn, Joanna D.; Ponsford, Amy H.; Sanderson, Christopher M.

doi:10.1042/bst20150014

Cited by 933 publications

(718 citation statements)

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“…Reactive oxygen species generation and oxidative stress are also implicated in pro‐inflammatory signaling cascades with extensive cross talk between NF‐ĸB and the antioxidant response transcription factor nrf2 reported (Wardyn et al., 2015). In this study, increased expression of HMOX1 and Sequestosome‐1 suggest activated nrf2 signaling.…”

Section: Discussionmentioning

confidence: 99%

“…For this reason, cellular copper levels are strictly maintained (Nevitt et al., 2012). ROS in cells, normally a result of electron leakage from mitochondria, are involved in many cellular signaling pathways, but increased levels result in oxidative stress and inflammatory responses (Shao et al., 2018; Uriu‐Adams & Keen, 2005) with significant cross talk in transcription factors controlling these responses, namely nrf2 and NF‐κB (Wardyn, Ponsford, & Sanderson, 2015). …”

Section: Introductionmentioning

confidence: 99%

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Acute exposure to organic and inorganic sources of copper: Differential response in intestinal cell lines

Keenan

O’Sullivan

Henry

et al. 2018

Food Science & Nutrition

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ScopeCopper supplementation in nutrition has evolved from using inorganic mineral salts to organically chelated minerals but with limited knowledge of the impact at the cellular level.MethodsHere, the impact of inorganic and organic nutrient forms (glycinate, organic acid, and proteinate) of copper on the cellular level is investigated on intestinal cell lines, HT29 and Caco‐2, after a 2‐hr acute exposure to copper compounds and following a 10‐hr recovery.ResultsFollowing the 10‐hr recovery, increases were observed in proteins involved in metal binding (metallothioneins) and antioxidant response (sulfiredoxin 1 and heme oxygenase 1), and global proteomic analysis suggested recruitment of the unfolded protein response and proteosomal overloading. Copper organic acid chelate, the only treatment to show striking and sustained reactive oxygen species generation, had the greatest impact on ubiquitinated proteins, reduced autophagy, and increased aggresome formation, reducing growth in both cell lines. The least effect was noted in copper proteinate with negligible impact on aggresome formation or extended growth for either cell line.ConclusionThe type and source of copper can impact significantly at the cellular level.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Acute exposure to organic and inorganic sources of copper: Differential response in intestinal cell lines

Keenan

O’Sullivan

Henry

et al. 2018

Food Science & Nutrition

View full text Add to dashboard Cite

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“…One of the target genes of Nrf2 produces heme oxygenase 1 (HMOX1). HMOX1 upregulation can lead to inhibition of NF-κB-mediated transcription [117]. Indeed, activation of Nrf2 by some drugs (e.g.…”

Section: Discussionmentioning

confidence: 99%

Unraveling cellular pathways contributing to drug-induced liver injury by dynamical modeling

Kuijper

Yang

Water

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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Introduction: Drug-induced liver injury (DILI) is a significant threat to human health and a major problem in drug development. It is hard to predict due to its idiosyncratic nature and which does not show up in animal trials. Hepatic adaptive stress response pathway activation is generally observed in drug-induced liver injury. Dynamical pathway modeling has the potential to foresee adverse effects of drugs before they go in trial. Ordinary differential equation modeling can offer mechanistic insight, and allows us to study the dynamical behavior of stress pathways involved in DILI. Areas covered: This review provides an overview on the progress of the dynamical modeling of stress and death pathways pertinent to DILI, i.e. pathways relevant for oxidative stress, inflammatory stress, DNA damage, unfolded proteins, heat shock and apoptosis. We also discuss the required steps for applying such modeling to the liver. Expert opinion: Despite the strong progress made since the turn of the century, models of stress pathways have only rarely been specifically applied to describe pathway dynamics for DILI. We argue that with minor changes, in some cases only to parameter values, many of these models can be repurposed for application in DILI research. Combining both dynamical models with in vitro testing might offer novel screening methods for the harmful side-effects of drugs. ARTICLE HISTORY

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“…Durante a inflamação crônica, diversas células imunológicas são continuamente ativadas por mediadores inflamatórios, e quando não ocorre resolução da inflamação, as próprias células recrutadas pelos mediadores inflamatórios secretam mais mediadores inflamatórios, gerando um ciclo vicioso que ativa o NFκB de forma crônica O ciclo vicioso gerado pela não resolução da inflamação pode ser interrompido pela ativação do Nrf2 21 . De maneira geral, o Nrf2 regula negativamente a transcrição de citocinas e quimiocinas pró-inflamatórias, moléculas de adesão celular, metaloproteinases e outros mediadores inflamatórios, como COX-2 e iNOS, que afetam direta ou indiretamente a ativação do NFκB e de outras rotas que controlam a inflamação 22 . Na verdade, as vias de sinalização do Nrf2 e do NFκB interagem de forma complementar e especializada para a manutenção da homeostase celular.…”

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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Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways

Cited by 933 publications

References 51 publications

Acute exposure to organic and inorganic sources of copper: Differential response in intestinal cell lines

Acute exposure to organic and inorganic sources of copper: Differential response in intestinal cell lines

Unraveling cellular pathways contributing to drug-induced liver injury by dynamical modeling

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

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