The receptor for advanced glycation end-products (RAGE) is an important pattern recognition receptor (PRR) for inflammaging

Teissier, Thibault; Boulanger, Éric

doi:10.1007/s10522-019-09808-3

Cited by 121 publications

(94 citation statements)

References 231 publications

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“…Advanced glycation end products (AGEs) plays a central role in the pathogenesis of DR and were found elevated in diabetes, since they originate from the reaction between a nucleophile, such as the amino group of a lysine, and a reducing sugars [ 50 ]. AGEs induce cell damage through binding to the AGE receptor (RAGE), expressed by different cells and comprised of three Ig domains that form its extracellular part [ 51 , 52 ]. Upon activation by its ligand, RAGE may trigger different and complex signaling pathways including the phosphatidylinositol 3-kinase (PI3K)/AKT pathway and the mitogen-activated protein kinases (MAPK) extracellular-signal-regulated kinases (ERK) 1/2 [ 53 , 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

Activation of the VEGF-A/ERK/PLA2 Axis Mediates Early Retinal Endothelial Cell Damage Induced by High Glucose: New Insight from an In Vitro Model of Diabetic Retinopathy

Giurdanella

Lupo

Gennuso

et al. 2020

IJMS

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Early blood retinal barrier (BRB) dysfunction induced by hyperglycemia was related to increased pro-inflammatory activity of phospholipase A2 (PLA2) and the upregulation of vascular endothelial growth factor A (VEGF-A). Here, we tested the role of VEGF-A in high glucose (HG)-induced damage of human retinal endothelial cells (HRECs) mediated by Ca++-dependent (cPLA2) and Ca++-independent (iPLA2) PLA2s. HRECs were treated with normal glucose (5 mM, NG) or high glucose (25 mM, HG) for 48 h with or without the VEGF-trap Aflibercept (Afl, 40 µg/mL), the cPLA2 inhibitor arachidonoyl trifluoromethyl ketone (AACOCF3; 15 µM), the iPLA2 inhibitor bromoenol lactone (BEL; 5 µM), or VEGF-A (80 ng/mL). Both Afl and AACOCF3 prevented HG-induced damage (MTT and LDH release), impairment of angiogenic potential (tube-formation), and expression of VEGF-A mRNA. Furthermore, Afl counteracted HG-induced increase of phospho-ERK and phospho-cPLA2 (immunoblot). VEGF-A in HG-medium increased glucose toxicity, through upregulation of phospho-ERK, phospho-cPLA2, and iPLA2 (about 55%, 45%, and 50%, respectively); immunocytochemistry confirmed the activation of these proteins. cPLA2 knockdown by siRNA entirely prevented cell damage induced by HG or by HG plus VEGF-A, while iPLA2 knockdown produced a milder protective effect. These data indicate that VEGF-A mediates the early glucose-induced damage in retinal endothelium through the involvement of ERK1/2/PLA2 axis activation.

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Section: Discussionmentioning

confidence: 99%

Activation of the VEGF-A/ERK/PLA2 Axis Mediates Early Retinal Endothelial Cell Damage Induced by High Glucose: New Insight from an In Vitro Model of Diabetic Retinopathy

Giurdanella

Lupo

Gennuso

et al. 2020

IJMS

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“…As humans age, the immune system becomes less efficient and the prevalence of both the inflammation related diseases diabetes and periodontitis increases [109,110].…”

Section: Inflammation and ''Inflammaging"mentioning

confidence: 99%

IDF Diabetes Atlas: Diabetes and oral health – A two-way relationship of clinical importance

Borgnakke

2019

Diabetes Research and Clinical Practice

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The current scientific evidence for the bi-directional associations between oral health and diabetes is summarized. The universal biologic mechanisms and demographic and behavioral risk drivers underlying these associations in both directions are also described. Dysglycemia, even slightly elevated blood sugar levels, adversely affects oral health, manifesting itself in several oral diseases and conditions. In the opposite direction, any oral infection with its subsequent local and systemic inflammatory responses adversely affects blood glucose levels. Moreover, painful, mobile, or missing teeth may lead to intake of soft food items representing a sub-optimal diet and hence poor nutrition, and thereby contribute to incident type 2 diabetes or to poorer glucose control in existing diabetes. Treatment of inflammation related oral conditions, such as non-surgical periodontal treatment and extraction of infected teeth, can lead to a clinically significant decrease in blood glucose levels. Attention to infectious oral diseases and referral to dental care professionals for treatment can therefore be an important novel tool for medical care professionals in preventing and managing diabetes mellitus. Dental professionals can detect unrecognized potential dysglycemia and refer for medical examination. Such interprofessional, patient centered care may contribute to improved health, wellbeing, and quality of life in people with diabetes.

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“…Glycation is enhanced when glucose levels are high, when dicarbonyls deriving from glycolytic intermediates or lipid peroxidation accumulate (Nigro et al, 2019), or when dicarbonyl detoxification by glyoxalases such as glyoxalase 1 (GLO1) and protein deglycase DJ-1 is low (Nigro et al, 2017). AGE formation may alter structure and function of the targeted proteins and, in addition, AGEs may elicit their effects as ligands of the pro-inflammatory receptor for advanced glycation end products (RAGE) (Teissier and Boulanger, 2019). One of the most abundant AGEs in vivo is N(6)-carboxymethyllysine (CML), whose formation is triggered, among other routes, by glyoxal (Brings et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Mapping sites of carboxymethyllysine modification on proteins reveals its consequences for proteostasis and cell proliferation

Sanzo

Spengler

Leheis

et al. 2020

Preprint

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Posttranslational mechanisms play a key role in modifying the abundance and function of cellular proteins. Among these, modification by advanced glycation end products (AGEs) has been shown to accumulate during aging and age-associated diseases but specific protein targets and functional consequences remain largely unexplored. Here, we devised a proteomic strategy to identify specific sites of carboxymethyllysine (CML) modification, one of the most abundant AGEs. We identified over 1000 sites of CML modification in mouse and primary human cells treated with the glycating agent glyoxal. By using quantitative proteomics, we found that protein glycation triggers a proteotoxic response and directly affects the protein degradation machinery. We show that glyoxal induces cell cycle perturbation in primary endothelial cells and that CML modification reduces acetylation of tubulins and impairs microtubule dynamics. Our data demonstrate the relevance of AGE modification for cellular function and pinpoint specific protein networks that might become compromised during aging.

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The receptor for advanced glycation end-products (RAGE) is an important pattern recognition receptor (PRR) for inflammaging

Cited by 121 publications

References 231 publications

Activation of the VEGF-A/ERK/PLA2 Axis Mediates Early Retinal Endothelial Cell Damage Induced by High Glucose: New Insight from an In Vitro Model of Diabetic Retinopathy

Activation of the VEGF-A/ERK/PLA2 Axis Mediates Early Retinal Endothelial Cell Damage Induced by High Glucose: New Insight from an In Vitro Model of Diabetic Retinopathy

IDF Diabetes Atlas: Diabetes and oral health – A two-way relationship of clinical importance

Mapping sites of carboxymethyllysine modification on proteins reveals its consequences for proteostasis and cell proliferation

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