scholarly journals Notch/NICD/RBP-J Signaling Axis Regulates M1 Polarization of Macrophages Mediated by Advanced Glycation End Products

2021 ◽  
Author(s):  
Hao Tan ◽  
Wenjie Xu ◽  
Xiaoqian Ding ◽  
Huayu Ye ◽  
Yun Hu ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Nuclear Translocation ◽  
Bone Diseases ◽  
Advanced Glycation ◽  
Raw264.7 Macrophages ◽  
Macrophages Polarization ◽  
M1 Polarization ◽  
Glycation End Products ◽  
End Products ◽  
Signaling Axis

Abstract Advanced glycation end products (AGEs) aggregation and macrophages polarization both play essential roles in degenerative bone diseases caused by aging or diabetes, such as senile or diabetic osteoporosis. Here, we aimed to understand the involvement and potential mechanism of AGEs in macrophages polarization and osteoclastogenesis. We found that RAW264.7 macrophages treated with AGEs highly expressed M1-associated genes and surface antigen markers CD86, and released a large amount of NO to the extracellular environment. Through the detection of osteoclast-related markers and TRAP staining, we revealed that the osteoclastogenesis of M1 macrophages could be markedly enhanced by AGEs. To explore the potential mechanisms of AGEs-mediated M1 polarization, we first demonstrated that AGEs effectively activated the transduction of Notch signaling pathway, including nuclear translocation of NICD1. Subsequently, it was observed that the M1 polarization effects induced by AGEs were significantly mitigated, when γ-secretase inhibitor DAPT and siRNA targeting silencing RBP-J were applied to block the signal transduction of Notch. In conclusion, our findings revealed a series of phenomena that AGEs induce macrophage M1 polarization and enhance its osteoclastogenesis ability, and Notch/NICD/RBP-J signaling axis is involved in the regulation of this polarization process.

Mangiferin suppressed advanced glycation end products (AGEs) through NF-κB deactivation and displayed anti-inflammatory effects in streptozotocin and high fat diet-diabetic cardiomyopathy rats

2016 ◽  
Vol 94 (3) ◽  
pp. 332-340 ◽  
Author(s):  
Jun Hou ◽  
Dezhi Zheng ◽  
Gabriel Fung ◽  
Haoyu Deng ◽  
Lin Chen ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Diabetic Cardiomyopathy ◽  
Advanced Glycation End Products ◽  
High Fat Diet ◽  
Nuclear Translocation ◽  
High Fat ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Mrna And Protein Expression

Given the importance of the aggregation of advanced glycation end products (AGEs) and cardiac inflammation in the onset and progression of diabetic cardiomyopathy (DCM), our objective in this study was to demonstrate the cardioprotective effect of mangiferin, an antidiabetic and anti-inflammatory agent, on diabetic rat model. The DCM model was established by a high-fat diet and a low dose of streptozotocin. DCM rats were treated orally with mangiferin (20 mg/kg) for 16 weeks. Serum and left ventricular myocardium were collected for determination of inflammatory cytokines. AGEs mRNA and protein expression of nuclear factor kappa B (NF-κB) and receptor for AGEs (RAGE) in myocardium were assayed by real-time PCR and Western blot. ROS levels were measured by dihydroethidium fluorescence staining. NF-κB binding activity was assayed by TransAM NF-κB p65 ELISA kit. Chronic treatment with mangiferin decreased the levels of myocardial enzymes (CK-MB, LDH) and inflammatory mediators (TNF-α, IL-1β). Meanwhile, NF-κB is inhibited by the reduction of nuclear translocation of p65 subunit, and mangiferin reduced AGE production and decreased the mRNA and protein expression of RAGE in DCM rats. Our data indicated that mangiferin could significantly ameliorate DCM by preventing the release of inflammatory cytokines, and inhibiting ROS accumulation, AGE/RAGE production, and NF-κB nuclear translocation, suggesting that mangiferin treatment might be beneficial in DCM.

Peanut skin polyphenols inhibit toxicity induced by advanced glycation end-products in RAW264.7 macrophages

2020 ◽  
Vol 145 ◽  
pp. 111619
Author(s):  
Annayara Celestina Ferreira Fernandes ◽  
Natália Carolina Vieira ◽  
Ádina Lima de Santana ◽  
Renata Luana de Pádua Gandra ◽  
Camila Rubia ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Peanut Skin ◽  
Raw264.7 Macrophages ◽  
Glycation End Products ◽  
End Products

scholarly journals Advanced Glycation End-Products and Hyperglycemia Increase Angiopoietin-2 Production by Impairing Angiopoietin-1-Tie-2 System

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Alessandra Puddu ◽  
Roberta Sanguineti ◽  
Davide Maggi ◽  
Massimo Nicolò ◽  
Carlo E. Traverso ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Intracellular Signaling ◽  
Nuclear Translocation ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Angiopoietin 2 ◽  
Angiopoietin 1

The angiopoietin-Tie-2 system plays a crucial role in the maintenance of endothelial integrity. Hyperglycemia and advanced glycation end-products (AGEs) are involved in endothelial cell dysfunction responsible of the pathogenesis of microvascular complications of diabetes. Here, we investigated whether glycated serum (GS) or hyperglycemia (HG) affect the angiopoietin-Tie-2 system in the microvascular endothelial cells HMEC-1. We found that culture for 5 days in the presence of AGEs and HG (alone or in combination) decreased cell proliferation, increased reactive oxygen species (ROS) production, and reduced ratio between the oxidized and the reduced form of glutathione. Since angiopoietin-1 (Ang-1) signaling regulates angiopoietin-2 (Ang-2) expression through inactivation of the forkhead transcription factor FoxO1, we investigated intracellular signaling of Ang-1 and expression of Ang-2. HG and AGEs reduced phosphorylation of Akt and abrogated phosphorylation of FoxO1 induced by Ang-1 without affecting neither Tie-2 expression nor its activation. Furthermore, AGEs and/or HG induced nuclear translocation of FoxO1 and increased Ang-2 production. In conclusion, we demonstrated that both hyperglycemia and AGEs affect the angiopoietin-Tie-2 system by impairing Ang-1/Tie-2 signaling and by increasing Ang-2 expression. These results suggest that therapeutic strategies useful in preventing or delaying the onset of diabetic vascular complications should be aimed to preserve Ang-1 signaling.

scholarly journals In Vitro Evaluation of the Toxicological Profile and Oxidative Stress of Relevant Diet-Related Advanced Glycation End Products and Related 1,2-Dicarbonyls

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Vanesa Cepas ◽  
Friederike Manig ◽  
Juan C. Mayo ◽  
Michael Hellwig ◽  
Debora Collotta ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amino Acids ◽  
Cell Death ◽  
Advanced Glycation End Products ◽  
Intracellular Signaling ◽  
Nuclear Translocation ◽  
Advanced Glycation ◽  
Dicarbonyl Compounds ◽  
Glycation End Products ◽  
End Products

During food processing and storage, and in tissues and fluids under physiological conditions, the Maillard reaction occurs. During this reaction, reactive 1,2-dicarbonyl compounds arise as intermediates that undergo further reactions to form advanced glycation end products (AGEs). Diet is the primary source of exogenous AGEs. Endogenously formed AGEs have been proposed as a risk factor in the pathogenesis of diet-related diseases such as diabetes, insulin resistance, cardiovascular diseases, or chronic disease. AGEs may differently contribute to the diet-related exacerbation of oxidative stress, inflammation, and protein modifications. Here, to understand the contribution of each compound, we tested individually, for the first time, the effect of five 1,2-dicarbonyl compounds 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 3,4-dideoxyglucosone-3-ene (3,4-DGE), glyoxal (GO), and methylglyoxal (MGO) and four different glycated amino acids N-ε-(carboxyethyl)lysine (CEL), N- ε -(carboxymethyl)lysine (CML), methylglyoxal-derived hydroimidazolone-1 (MG-H1), and pyrraline (Pyrr) in a cell line of human keratinocytes (HaCaT). We found that most of the glycated amino acids, i.e., CEL, CML, and MG-H1, did not show any cytotoxicity. At the same time, 1,2-dicarbonyl compounds 3-DGal, 3,4-DGE, GO, and MGO increased the production of reactive oxygen species and induced cell death. MGO induced cell death by apoptosis, whereas 3-DGal and 3,4-DGE induced nuclear translocation of the proinflammatory NF-κB transcription pathway, and the activation of the pyroptosis-related NLRP3 inflammasome cascade. Overall, these results demonstrate the higher toxic impact of 1,2-dicarbonyl compounds on mucosal epithelial cells when compared to glycated amino acids and the selective activation of intracellular signaling pathways involved in the crosstalk mechanisms linking oxidative stress to excessive inflammation.

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