Advanced glycation end products and its receptor (RAGE) are increased in patients with COPD

Lian, Wei; Ma, Li; Nicholson, Louise; Black, Peter

doi:10.1016/j.rmed.2010.11.001

Cited by 106 publications

(107 citation statements)

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“…The concentration of AGEs in smokers, who are predisposed to developing COPD, is significantly higher than in nonsmokers (41). There is also an inverse relationship between AGE and sRAGE expression level in the BAL fluid of smokers and nonsmokers.…”

Section: Ages: Predictive Biomarkers For Lung Disease?mentioning

confidence: 91%

Receptor for Advanced Glycation End-Products Regulates Lung Fluid Balance via Protein Kinase C–gp91^phox Signaling to Epithelial Sodium Channels

Downs

Kreiner

Johnson

et al. 2015

Am J Respir Cell Mol Biol

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The receptor for advanced glycation end-products (RAGE), a multiligand member of the Ig family, may play a crucial role in the regulation of lung fluid balance. We quantified soluble RAGE (sRAGE), a decoy isoform, and advanced glycation end-products (AGEs) from the bronchoalveolar lavage fluid of smokers and nonsmokers, and tested the hypothesis that AGEs regulate lung fluid balance through protein kinase C (PKC)-gp91 phox signaling to the epithelial sodium channel (ENaC). Human bronchoalveolar lavage samples from smokers showed increased AGEs (9.02 6 3.03 mg versus 2.48 6 0.53 mg), lower sRAGE (1,205 6 292 pg/ml versus 1,910 6 263 pg/ml), and lower volume(s) of epithelial lining fluid (97 6 14 ml versus 133 6 17 ml). sRAGE levels did not predict ELF volumes in nonsmokers; however, in smokers, higher volumes of ELF were predicted with higher levels of sRAGE. Single-channel patch clamp analysis of rat alveolar epithelial type 1 cells showed that AGEs increased ENaC activity measured as the product of the number of channels (N) and the open probability (Po) (NPo) from 0.19 6 0.08 to 0.83 6 0.22 (P = 0.017) and the subsequent addition of 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine-N-oxyl decreased ENaC NPo to 0.15 6 0.07 (P = 0.01). In type 2 cells, human AGEs increased ENaC NPo from 0.12 6 0.05 to 0.53 6 0.16 (P = 0.025) and the addition of 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine-N-oxyl decreased ENaC NPo to 0.10 6 0.03 (P = 0.013). Using molecular and biochemical techniques, we observed that inhibition of RAGE and PKC activity attenuated AGE-induced activation of ENaC. AGEs induced phosphorylation of p47 phox and increased gp91 phox -dependent reactive oxygen species production, a response that was abrogated with RAGE or PKC inhibition. Finally, tracheal instillation of AGEs promoted clearance of lung fluid, whereas concomitant inhibition of RAGE, PKC, and gp91 phox abrogated the response.Keywords: acute respiratory distress syndrome; chronic obstructive pulmonary disease; pulmonary edema; alveolar microenvironment; lung injury Clinical RelevanceReceptor for advanced glycation end-products (RAGE) plays a critical role in regulating inflammation in the lung and may be a therapeutic target in the treatment of acute and chronic lung diseases. Herein we describe the signal transduction pathway through which RAGE regulates the epithelial sodium channel.

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Section: Ages: Predictive Biomarkers For Lung Disease?mentioning

confidence: 91%

Receptor for Advanced Glycation End-Products Regulates Lung Fluid Balance via Protein Kinase C–gp91^phox Signaling to Epithelial Sodium Channels

Downs

Kreiner

Johnson

et al. 2015

Am J Respir Cell Mol Biol

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“…Various studies showed that AGEs impaired vascular function by accumulating in the vessel wall and by quenching the nitric oxide released as an endogenous vasodilatatory and antithrombotic molecule, thereby potentially impacting on vascular relaxation and function. AGEs bound to their specific receptors (RAGE) in the endothelium triggered the production of reactive oxygen intermediates [39][40][41][42]. Therefore, AGEs induce vascular pathological changes through direct and also through an indirect (redox stress) mechanism.…”

Section: Discussionmentioning

confidence: 99%

In vitro effects of prolonged exposure to quercetin and epigallocatechin gallate of the peripheral blood mononuclear cell membrane

Margină

Ilie

Manda

et al. 2014

Cellular and Molecular Biology Letters

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Abstract:The study aimed to assess biophysical changes that take place in the peripheral blood mononuclear cell (PBMC) membranes when exposed in vitro to 10 µM quercetin or epigallocatechin gallate (EGCG) for 24 and 48 h. PBMCs isolated from hypercholesterolemia patients were compared to those from normocholesterolemia subjects. The membrane fluidity and transmembrane potential were evaluated and the results were correlated with biochemical parameters relevant to oxidative stress, assessed in the patients' plasma. The baseline value of PBMC membrane anisotropy for the hypercholesterolemia patients was lower than that of the control group. These results correlated with the plasma levels of advanced glycation end products, which were significantly higher in the hypercholesterolemia group, and the total plasma antioxidant status, which was significantly higher in normocholesterolemia subjects. In the case of normocholesterolemia cells in vitro, polyphenols induced a decrease in membrane anisotropy (7.25-11.88% at 24 h, 1.82-2.26% at 48 h) and a hyperpolarizing effect (8.30-8.90% at 24 h and 4.58-13.00% at 48 h). The same effect was induced in hypercholesterolemia cells, but only after 48 h exposure to the polyphenols: the decrease in membrane anisotropy was 5.70% for quercetin and 2.33% for EGCG. After 48 h of in vitro incubation with the polyphenols, PBMCs isolated from hypercholesterolemia patients exhibited the effects that had been registered in cells from normocholesterolemia subjects after 24 h exposure. These results outlined the beneficial action of the studied polyphenols, quercetin and EGCG, as dietary supplements in normocholesterolemia and hypercholesterolemia patients.

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“…tory tool for the interaction between RAGE and TIRAP may efficiently abrogate RAGE-mediated signaling regardless of ligand species. RAGE has been demonstrated to play a significant role in the development of several degenerative and inflammation-related diseases (8,15,(17)(18)(19)(20)(21)(22). In the present study, we monitored cellular behavior related with two pathological conditions, neuronal cell death and the migration and invasion of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, with the exception of the skin and lungs, RAGE expression is kept at low levels in the adult body (13,14). The binding of ligands and the increased expression of RAGE potentially lead to inflammation-associated pathological conditions, such as those found in neurodegenerative diseases (8,15,16), cardiovascular and renal diseases (17,18), pulmonary diseases (19), diabetes and metabolic disorders (20,21), as well as cancer (22). Under such conditions, NF-κB activated by RAGE signaling enhances the expression of RAGE, thus composing a self-sustaining positive feedback loop.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of RAGE signaling through the intracellular delivery of inhibitor peptides by PEI cationization

Putranto

Murata

Kataoka

et al. 2013

International Journal of Molecular Medicine

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Abstract. The receptor for advanced glycation end products (RAGE) is a multi-ligand cell surface receptor and a member of the immunoglobulin superfamily. RAGE is involved in a wide range of inflammatory, degenerative and hyper-proliferative disorders which span over different organs by engaging diverse ligands, including advanced glycation end products, S100 family proteins, high-mobility group protein B1 (HMGB1) and amyloid β. We previously demonstrated that the cytoplasmic domain of RAGE is phosphorylated upon the binding of ligands, enabling the recruitment of two distinct pairs of adaptor proteins, Toll-interleukin 1 receptor domain-containing adaptor protein (TIRAP) and myeloid differentiation protein 88 (MyD88). This engagement allows the activation of downstream effector molecules, and thereby mediates a wide variety of cellular processes, such as inflammatory responses, apoptotic cell death, migration and cell growth. Therefore, inhibition of the binding of TIRAP to RAGE may abrogate intracellular signaling from ligand-activated RAGE. In the present study, we developed inhibitor peptides for RAGE signaling (RAGE-I) by mimicking the phosphorylatable cytosolic domain of RAGE. RAGE-I was efficiently delivered into the cells by polyethylenimine (PEI) cationization. We demonstrated that RAGE-I specifically bound to TIRAP and abrogated the activation of Cdc42 induced by ligand-activated RAGE. Furthermore, we were able to reduce neuronal cell death induced by an excess amount of S100B and to inhibit the migration and invasion of glioma cells in vitro. Our results indicate that RAGE-I provides a powerful tool for therapeutics to block RAGE-mediated multiple signaling. IntroductionThe receptor for advanced glycation end products (RAGE) belongs to the immunoglobulin superfamily of cell surface receptors. It comprises of three domains, an extracellular domain (with one V-type and two C-type domains), a transmembrane-spanning domain and a cytoplasmic domain (1). RAGE is activated by binding to a diverse repertoire of ligands (2). These ligands include advanced glycation end products (AGEs) (3), S100 family proteins (4-6), high-mobility group box 1 (HMGB1) (5,7) and amyloid β (Aβ) peptides (8). Activated RAGE triggers multiple intracellular pathways, such as the production of reactive oxygen species, the activation of p21ras, Erk1/2 (p44/p42) mitogen-activated protein kinases, p38 and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases, rhoGTPases, phosphatidylinositol-3 kinase and Janus kinase (JAK)/signal transducers and activators of transcription (STAT), eventually leading to the activation of nuclear factor-κB (NF-κB), activator protein-1 (AP-1) and .RAGE is physiologically expressed in multiple tissues during embryonic development, but is mostly downregulated as cells reach homeostasis in adult life. Therefore, with the exception of the skin and lungs, RAGE expression is kept at low levels in the adult body (13,14). The binding of ligands and the increased expr...

show abstract

Advanced glycation end products and its receptor (RAGE) are increased in patients with COPD

Abstract: The increased staining for both AGEs and RAGE in COPD lung raises the possibility that the RAGE-AGEs interaction may have a role in the pathogenesis of COPD.

Cited by 106 publications

References 45 publications

Receptor for Advanced Glycation End-Products Regulates Lung Fluid Balance via Protein Kinase C–gp91^phox Signaling to Epithelial Sodium Channels

Receptor for Advanced Glycation End-Products Regulates Lung Fluid Balance via Protein Kinase C–gp91^phox Signaling to Epithelial Sodium Channels

In vitro effects of prolonged exposure to quercetin and epigallocatechin gallate of the peripheral blood mononuclear cell membrane

Inhibition of RAGE signaling through the intracellular delivery of inhibitor peptides by PEI cationization

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Advanced glycation end products and its receptor (RAGE) are increased in patients with COPD

Abstract: The increased staining for both AGEs and RAGE in COPD lung raises the possibility that the RAGE-AGEs interaction may have a role in the pathogenesis of COPD.

Cited by 106 publications

References 45 publications

Receptor for Advanced Glycation End-Products Regulates Lung Fluid Balance via Protein Kinase C–gp91phox Signaling to Epithelial Sodium Channels

Receptor for Advanced Glycation End-Products Regulates Lung Fluid Balance via Protein Kinase C–gp91phox Signaling to Epithelial Sodium Channels

In vitro effects of prolonged exposure to quercetin and epigallocatechin gallate of the peripheral blood mononuclear cell membrane

Inhibition of RAGE signaling through the intracellular delivery of inhibitor peptides by PEI cationization

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Product

Resources

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Receptor for Advanced Glycation End-Products Regulates Lung Fluid Balance via Protein Kinase C–gp91^phox Signaling to Epithelial Sodium Channels

Receptor for Advanced Glycation End-Products Regulates Lung Fluid Balance via Protein Kinase C–gp91^phox Signaling to Epithelial Sodium Channels