Crosstalk of reactive oxygen species and NF-κB signaling

Morgan, Michael J.; Liu, Zheng-gang

doi:10.1038/cr.2010.178

Cited by 2,683 publications

(2,081 citation statements)

References 161 publications

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“…A positive relationship between oxidative stress generation and activation of the pro‐inflammatory NF‐κB pathway has been described in different clinical conditions 29. One of the earliest events in NF‐κB pathway activation is the phosphorylation of p65 subunit.…”

Section: Resultsmentioning

confidence: 99%

Branched‐chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

Zhenyukh

González‐Amor

Rodrigues-Díez

et al. 2018

J Cellular Molecular Medi

112

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Branched‐chain amino acids (BCAA: leucine, isoleucine and valine) are essential amino acids implicated in glucose metabolism and maintenance of correct brain function. Elevated BCAA levels can promote an inflammatory response in peripheral blood mononuclear cells. However, there are no studies analysing the direct effects of BCAA on endothelial cells (ECs) and its possible modulation of vascular function. In vitro and ex vivo studies were performed in human ECs and aorta from male C57BL/6J mice, respectively. In ECs, BCAA (6 mmol/L) increased eNOS expression, reactive oxygen species production by mitochondria and NADPH oxidases, peroxynitrite formation and nitrotyrosine expression. Moreover, BCAA induced pro‐inflammatory responses through the transcription factor NF‐κB that resulted in the release of intracellular adhesion molecule‐1 and E‐selectin conferring endothelial activation and adhesion capacity to inflammatory cells. Pharmacological inhibition of mTORC1 intracellular signalling pathway decreased BCAA‐induced pro‐oxidant and pro‐inflammatory effects in ECs. In isolated murine aorta, BCAA elicited vasoconstrictor responses, particularly in pre‐contracted vessels and after NO synthase blockade, and triggered endothelial dysfunction, effects that were inhibited by different antioxidants, further demonstrating the potential of BCAA to induce oxidative stress with functional impact. In summary, we demonstrate that elevated BCAA levels generate inflammation and oxidative stress in ECs, thereby facilitating inflammatory cells adhesion and endothelial dysfunction. This might contribute to the increased cardiovascular risk observed in patients with elevated BCAA blood levels.

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Section: Resultsmentioning

confidence: 99%

Branched‐chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

Zhenyukh

González‐Amor

Rodrigues-Díez

et al. 2018

J Cellular Molecular Medi

112

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“…This occurs despite the observed increase in NF‐ κ B activity, known to regulate the expression of several antioxidant proteins, including MnSOD (reviewed in Morgan and Liu 2011). H 2 O 2 can alter the redox state of the cell by either reacting directly with thiol residues within redox‐sensitive proteins or by shifting the GSH/GSSG ratio (Schafer and Buettner 2001).…”

Section: Discussionmentioning

confidence: 99%

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

et al. 2017

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Despite the fact that skeletal muscle insulin resistance is the hallmark of type‐2 diabetes mellitus (T2DM), inflexibility in substrate energy metabolism has been observed in other tissues such as liver, adipose tissue, and heart. In the heart, structural and functional changes ultimately lead to diabetic cardiomyopathy. However, little is known about the early biochemical changes that cause cardiac metabolic dysregulation and dysfunction. We used a dietary model of fructose‐induced T2DM (10% fructose in drinking water for 6 weeks) to study cardiac fatty acid metabolism in early T2DM and related signaling events in order to better understand mechanisms of disease. In early type‐2 diabetic hearts, flux through the fatty acid oxidation pathway was increased as a result of increased cellular uptake (CD36), mitochondrial uptake (CPT1B), as well as increased β‐hydroxyacyl‐CoA dehydrogenase and medium‐chain acyl‐CoA dehydrogenase activities, despite reduced mitochondrial mass. Long‐chain acyl‐CoA dehydrogenase activity was slightly decreased, resulting in the accumulation of long‐chain acylcarnitine species. Cardiac function and overall mitochondrial respiration were unaffected. However, evidence of oxidative stress and subtle changes in cardiolipin content and composition were found in early type‐2 diabetic mitochondria. Finally, we observed decreased activity of SIRT1, a pivotal regulator of fatty acid metabolism, despite increased protein levels. This indicates that the heart is no longer capable of further increasing its capacity for fatty acid oxidation. Along with increased oxidative stress, this may represent one of the earliest signs of dysfunction that will ultimately lead to inflammation and remodeling in the diabetic heart.

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“…Thus, ER stress and oxidative stress are intrinsically linked with each process triggering the other in differing scenarios encountered by the cell. Oxidative stress can lead to activation on inflammatory signalling pathways, including via activation of (1) the NFκB transcription factor that regulates inflammatory genes but also can regulate ROS/RNS production and degradation, and (2) the NRF2 transcription factor that primarily regulates the oxidative state of the cell but can also lead to inflammatory signalling 18, 19. Interpretation of studies of ROS/RNS on inflammatory activation pathways is complex as the large number of potential pathways affected by ROS/RNS means that both direct and indirect activation mechanisms occur.…”

Section: Introduction To Oxidative and Er Stressmentioning

confidence: 99%

Oxidative and endoplasmic reticulum stress in respiratory disease

2018

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Oxidative stress and endoplasmic reticulum (ER) stress are related states that can occur in cells as part of normal physiology but occur frequently in diseases involving inflammation. In this article, we review recent findings relating to the role of oxidative and ER stress in the pathophysiology of acute and chronic nonmalignant diseases of the lung, including infections, cystic fibrosis, idiopathic pulmonary fibrosis and asthma. We also explore the potential of drugs targeting oxidative and ER stress pathways to alleviate disease.

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Crosstalk of reactive oxygen species and NF-κB signaling

Cited by 2,683 publications

References 161 publications

Branched‐chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

Branched‐chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

Oxidative and endoplasmic reticulum stress in respiratory disease

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