scholarly journals Journey to a Receptor for Advanced Glycation End Products Connection in Severe Acute Respiratory Syndrome Coronavirus 2 Infection

2020 ◽  
Author(s):  
Divya Roy ◽  
Ravichandran Ramasamy ◽  
Ann Marie Schmidt
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Advanced Glycation End Products ◽  
Tissue Damage ◽  
Advanced Glycation ◽  
Molecular Pattern ◽  
Increased Risk ◽  
Glycation End Products ◽  
End Products ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide and the pandemic has yet to wane. Despite its associated significant morbidity and mortality, there are no definitive cures and no fully preventative measures to combat SARS-CoV-2. Hence, the urgency to identify the pathobiological mechanisms underlying increased risk for and the severity of SARS-CoV-2 infection is mounting. One contributing factor, the accumulation of damage-associated molecular pattern molecules, is a leading trigger for the activation of nuclear factor-kB and the IRF (interferon regulatory factors), such as IRF7. Activation of these pathways, particularly in the lung and other organs, such as the heart, contributes to a burst of cytokine release, which predisposes to significant tissue damage, loss of function, and mortality. The receptor for advanced glycation end products (RAGE) binds damage-associated molecular patterns is expressed in the lung and heart, and in priming organs, such as the blood vessels (in diabetes) and adipose tissue (in obesity), and transduces the pathological signals emitted by damage-associated molecular patterns. It is proposed that damage-associated molecular pattern-RAGE enrichment in these priming tissues, and in the lungs and heart during active infection, contributes to the widespread tissue damage induced by SARS-CoV-2. Accordingly, the RAGE axis might play seminal roles in and be a target for therapeutic intervention in SARS-CoV-2 infection.

scholarly journals The Effect of Glyceraldehyde-Derived Advanced Glycation End Products on β-Tubulin-Inhibited Neurite Outgrowth in SH-SY5Y Human Neuroblastoma Cells

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2958
Author(s):  
Ryuto Nasu ◽  
Ayako Furukawa ◽  
Keita Suzuki ◽  
Masayoshi Takeuchi ◽  
Yoshiki Koriyama
Keyword(s):  
Neurite Outgrowth ◽  
Advanced Glycation End Products ◽  
Neurological Disorders ◽  
Neuroblastoma Cells ◽  
Advanced Glycation ◽  
Human Neuroblastoma ◽  
Increased Risk ◽  
Glycation End Products ◽  
End Products ◽  
Β Tubulin

Nutritional factors can affect the risk of developing neurological disorders and their rate of progression. In particular, abnormalities of carbohydrate metabolism in diabetes mellitus patients lead to an increased risk of neurological disorders such as Alzheimer’s disease (AD). In this study, we investigated the relationship between nervous system disorder and the pathogenesis of AD by exposing SH-SY5Y neuroblastoma cells to glyceraldehyde (GA). We previously reported that GA-derived toxic advanced glycation end products (toxic AGEs, TAGE) induce AD-like alterations including intracellular tau phosphorylation. However, the role of TAGE and their target molecules in the pathogenesis of AD remains unclear. In this study, we investigated the target protein for TAGE by performing two-dimensional immunoblot analysis with anti-TAGE antibody and mass spectrometry and identified β-tubulin as one of the targets. GA treatment induced TAGE-β-tubulin formation and abnormal aggregation of β-tubulin, and inhibited neurite outgrowth in SH-SY5Y cells. On the other hand, glucose-derived AGEs were also involved in developing AD. However, glucose did not make abnormal aggregation of β-tubulin and did not inhibit neurite outgrowth. Understanding the underlying mechanism of TAGE-β-tubulin formation by GA and its role in neurodegeneration may aid in the development of novel therapeutics and neuroprotection strategies.

scholarly journals Shorter Telomere Length in Carriers of APOE-ε4 and High Plasma Concentration of Glucose, Glyoxal and Other Advanced Glycation End Products (AGEs)

2019 ◽  
Vol 75 (10) ◽  
pp. 1894-1898 ◽  
Author(s):  
Varinderpal S Dhillon ◽  
Permal Deo ◽  
Ann Chua ◽  
Phil Thomas ◽  
Michael Fenech
Keyword(s):  
Risk Factor ◽  
Telomere Length ◽  
Advanced Glycation End Products ◽  
Biological Aging ◽  
Advanced Glycation ◽  
Apoe Ε4 ◽  
Increased Risk ◽  
Glycation End Products ◽  
End Products ◽  
Ε4 Allele

Abstract Apolipoprotein-ε4 (APOE-ε4)—common variant is a major genetic risk factor for cognitive decline and Alzheimer's disease (AD). An accelerated rate of biological aging could contribute to this increased risk. Glycation of serum proteins due to excessive glucose and reactive oxygen species leads to the formation of advanced glycation end products (AGEs)—a risk factor for diabetes and AD, and decline in motor functioning in elderly adults. Aim of present study was to investigate impact of APOE-ε4 allele containing genotype and accumulation of AGEs in plasma on telomere length (TL). Results showed that TL is significantly shorter in APOE-ε4 carriers compared with non-APOE-ε4 carriers (p = .0003). Higher plasma glucose level was associated with shorter TL irrespective of APOE-ε4 allele containing genotype (r = −.26; p = .0004). With regard to AGEs, higher plasma glyoxal and fluorescent AGEs concentrations were inversely related to TL (r = −.16; p = .03; r = −.28; p = .0001), however, plasma Nε-(carboxymethyl)lysine levels didn't correlate with TL (r = −.04; p = .57). Results support the hypotheses that APOE-ε4 carriers have shorter telomeres than noncarriers and telomere erosion is increased with higher concentration of glucose, fluorescent AGEs, and glyoxal.

scholarly journals On the Significance of New Biochemical Markers for the Diagnosis of Premature Labour

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Rafał Rzepka ◽  
Barbara Dołęgowska ◽  
Aleksandra Rajewska ◽  
Sebastian Kwiatkowski
Keyword(s):  
Acute Inflammation ◽  
Preterm Labour ◽  
Premature Labour ◽  
Advanced Glycation ◽  
Chronic Inflammatory Response ◽  
Glycation End Products ◽  
End Products ◽  
Stromal Cell Derived Factor ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Preterm labour is defined as a birth taking place between 22nd and 37th weeks of gestation. Despite numerous studies on the aetiology and pathogenesis of preterm labour, its very cause still remains unclear. The importance of the cytokines and acute inflammation in preterm labour aetiology is nowadays well-proven. However, chronic inflammation as an element of the pathogenesis of premature labour is still unclear. This paper presents a literature review on the damage-associated molecular patterns (DAMPs), receptors for advanced glycation end products (RAGE), negative soluble isoforms of RAGE, chemokine-stromal cell-derived factor-1 (SDF-1) and one of the adipokines, resistin, in the pathogenesis of preterm labour. We conclude that the chronic inflammatory response can play a much more important role in the pathogenesis of preterm delivery than the acute one.

scholarly journals Endothelial Dysfunction and Advanced Glycation End Products in Patients with Newly Diagnosed Versus Established Diabetes: From the CORDIOPREV Study

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 238
Author(s):  
Silvia de la Cruz-Ares ◽  
Magdalena P. Cardelo ◽  
Francisco M. Gutiérrez-Mariscal ◽  
José D. Torres-Peña ◽  
Antonio García-Rios ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Advanced Glycation End Products ◽  
Intima Media Thickness ◽  
Serum Levels ◽  
Atherosclerotic Cardiovascular Disease ◽  
Newly Diagnosed ◽  
Advanced Glycation ◽  
Increased Risk ◽  
Glycation End Products ◽  
End Products

Endothelial dysfunction and intima-media thickness of common carotid arteries (IMT-CC) are considered subclinical markers of atherosclerotic cardiovascular disease (ASCVD). Advanced glycation end products (AGEs) are increased in type 2 diabetes mellitus (T2DM) patients, compared with non-diabetics, being implicated in micro- and macrovascular complications. Our aim was to compare serum AGEs levels and subclinical atherosclerotic markers between patients with established and newly diagnosed T2DM. Among 540 patients with T2DM and coronary heart disease from the CORDIOPREV study, 350 patients had established T2DM and 190 patients had newly diagnosed T2DM. Serum levels of AGEs (methylglyoxal (MG) and N-carboxymethyl lysine (CML)) and subclinical atherosclerotic markers (brachial flow-mediated vasodilation (FMD) and IMT-CC) were measured. AGEs levels (all p < 0.001) and IMT-CC (p = 0.025) were higher in patients with established vs. newly diagnosed T2DM, whereas FMD did not differ between the two groups. Patients with established T2DM and severe endothelial dysfunction (i.e., FMD < 2%) had higher serum MG levels, IMT-CC, HOMA-IR and fasting insulin levels than those with newly diagnosed T2DM and non-severe endothelial dysfunction (i.e., FMD ≥ 2%) (all p < 0.05). Serum CML levels were greater in patients with established vs. newly diagnosed T2DM, regardless of endothelial dysfunction severity. Serum AGEs levels and IMT-CC were significantly higher in patients with established vs. newly diagnosed T2DM, highlighting the progressively increased risk of ASCVD in the course of T2DM. Establishing therapeutic strategies to reduce AGEs production and delay the onset of cardiovascular complications in newly diagnosed T2DM patients or minimize ASCVD risk in established T2DM patients is needed.

scholarly journals Advanced Glycation End Products (AGEs), Receptor for AGEs, Diabetes, and Bone: Review of the Literature

2019 ◽  
Vol 3 (10) ◽  
pp. 1799-1818 ◽  
Author(s):  
Kamyar Asadipooya ◽  
Edilfavia Mae Uy
Keyword(s):  
Signaling Pathway ◽  
Advanced Glycation End Products ◽  
Cell Metabolism ◽  
Bone Cell ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Soluble Rage ◽  
Increased Risk ◽  
Glycation End Products ◽  
End Products

AbstractDiabetes compromises bone cell metabolism and function, resulting in increased risk of fragility fracture. Advanced glycation end products (AGEs) interact with the receptor for AGEs (RAGE) and can make a meaningful contribution to bone cell metabolism and/or alter function. Searches in PubMed using the key words “advanced glycation end-product,” “RAGE,” “sRAGE,” “bone,” and “diabetes” were made to explain some of the clinical outcomes of diabetes in bone metabolism through the AGE–RAGE signaling pathway. All published clinical studies were included in tables. The AGE–RAGE signaling pathway participates in diabetic complications, including diabetic osteopathy. Some clinical results in diabetic patients, such as reduced bone density, suppressed bone turnover markers, and bone quality impairment, could be potentially due to AGE–RAGE signaling consequences. However, the AGE–RAGE signaling pathway has some helpful roles in the bone, including an increase in osteogenic function. Soluble RAGE (sRAGE), as a ligand decoy, may increase in either conditions of RAGE production or destruction, and then it cannot always reflect the AGE–RAGE signaling. Recombinant sRAGE can block the AGE–RAGE signaling pathway but is associated with some limitations, such as accessibility to AGEs, an increase in other RAGE ligands, and a long half-life (24 hours), which is associated with losing the beneficial effect of AGE/RAGE. As a result, sRAGE is not a helpful marker to assess activity of the RAGE signaling pathway. The recombinant sRAGE cannot be translated into clinical practice due to its limitations.

Dietary advanced glycation end products (AGEs) and breast cancer mortality in the women’s health initiative (WHI).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1570-1570
Author(s):  
Lindsay Leuthen Peterson ◽  
Omonefe Omofuma ◽  
David P Turner ◽  
Anwar Merchant ◽  
Jiajia Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Advanced Glycation End Products ◽  
Mortality Risk ◽  
Advanced Glycation ◽  
Health Initiative ◽  
Increased Risk ◽  
Glycation End Products ◽  
End Products

1570 Background: Breast cancer (BrCa) is the second leading cause of cancer death and constitutes about 14% of total cancer deaths among US women. Advanced glycation end-products (AGEs) are implicated in chronic diseases including cancer and cardiovascular diseases (CVD). AGEs are naturally found in animal products and processed foods, and preparing food at high temperatures increases AGE formation. Our goal was to assess the association between post-diagnosis dietary NƐ-carboxymethyl-lysine (CML)-AGE intake, a common measure of AGE, and mortality from all-causes, BrCa and CVD among participants with invasive BrCa in the Women’s Health Initiative (WHI). Methods: The WHI enrolled postmenopausal women aged 50 to 79 years from 1993-1998 into randomized controlled trials and a prospective observational study to examine causes of morbidity and mortality. In this analysis, we included 2,073 women diagnosed with invasive BrCa during follow-up who completed a food frequency questionnaire (FFQ) after diagnosis, had energy intakes between ≥600 kcal/day and ≤5000 kcal/day, and had CML-AGE intake data available. Women were followed from BrCa diagnosis until death or censoring through March 2018. Cox proportional hazards regression models estimated the hazard ratios (HR) and 95% CIs of mortality risk from all-causes, BrCa and CVD by tertiles of dietary CML-AGE intake with adjustment for age, income, race/ethnicity, study arm, time from diagnosis to FFQ completion, education, physical activity, smoking, BMI, ER/PR status, diagnosis stage, postmenopausal hormone use, intake of energy, alcohol, fat, red and processed meats. Results: After a median 15.1 years of follow-up, 642 deaths were reported including 198 BrCa-specific and 129 CVD-specific deaths. The average time from BrCa diagnosis to FFQ completion was 1.5 years. Compared to the lowest tertile of CML-AGE intake, there was an increased risk in the highest tertile for all-cause mortality (HR: 1.51, 95% CI: 1.17-1.94), BrCa (HR: 1.86, 95% CI: 1.19-2.91) and CVD (HR: 2.14, 95% CI: 1.19-3.84) mortality. Conclusions: Higher dietary AGE intake after BrCa diagnosis in postmenopausal women was associated with increased risk of mortality from all-causes, BrCa and CVD. Exposure to AGEs could be modified through dietary counseling and evaluated in relation to reduced mortality risk after BrCa diagnosis.

Advanced glycation end products elicit externalization of phosphatidylserine in a subpopulation of platelets via 5-HT2A/2Creceptors

2007 ◽  
Vol 293 (1) ◽  
pp. C328-C336 ◽  
Author(s):  
Yingjie Wang ◽  
Werner Beck ◽  
Reinhold Deppisch ◽  
Sally M. Marshall ◽  
Nicholas A. Hoenich ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Inflammatory Responses ◽  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Coagulation Cascade ◽  
Dependent Manner ◽  
Advanced Glycation ◽  
Increased Risk ◽  
Glycation End Products ◽  
End Products

Advanced glycation end products (AGE) are substantially elevated in individuals with diabetes and/or chronic kidney disease (CKD). These patients are at greatly increased risk of cardiovascular events. The purpose of this study was to investigate the novel hypothesis that AGE elicit externalization of the platelet membrane phospholipid phosphatidylserine (PS). This contributes to hemostasis through propagation of the coagulation cascade leading to thrombus formation. Platelet-rich plasma (PRP) was prepared by differential centrifugation, and PS externalization was quantified by a fluorescence-activated cell sorter using annexin V-FITC. Human serum albumin (HSA)-AGE was generated by incubating HSA with glucose for 2, 4, or 6 wk, and total HSA-AGE was assessed by fluorescence intensity. The 2-wk HSA-AGE preparation (0–2 mg/ml) stimulated a concentration-dependent increase in PS externalization in a subpopulation of platelets that was threefold at 2 mg/ml. In contrast, the 4- and 6-wk preparations were maximal at 0.5 mg/ml and fivefold in magnitude. These effects mirrored the change in total HSA-AGE content of the preparations. The PS response was maximal at 10 min and inhibited by the PKC-δ inhibitor rottlerin and the serotonin [5-hydroxytryptamine (5-HT)]2A/2Creceptor antagonist ritanserin in a dose-dependent manner. Moreover, the 5-HT2A/2Creceptor agonist 1,2,5-dimethoxy-4-iodophenyl-2-aminopropane mimicked the effect of HSA-AGE on PS externalization. These data demonstrate, for the first time, that HSA-AGE stimulates PS externalization in a subpopulation of platelets via the 5-HT2A/2Creceptor. This may have important consequences for platelet involvement in inflammatory responses and the increased cardiovascular risk observed in individuals with diabetes and/or CKD.

scholarly journals Long Term Dietary Restriction of Advanced Glycation End-Products (AGEs) in Older Adults with Type 2 Diabetes Is Feasible and Efficacious-Results from a Pilot RCT

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3143
Author(s):  
Roni Lotan ◽  
Ithamar Ganmore ◽  
Shahar Shelly ◽  
Moran Zacharia ◽  
Jaime Uribarri ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Older Adults ◽  
Advanced Glycation End Products ◽  
Dietary Intervention ◽  
Advanced Glycation ◽  
Increased Risk ◽  
Glycation End Products ◽  
End Products

Introduction: High serum concentrations of advanced glycation end-products (AGEs) in older adults and diabetics are associated with an increased risk of cognitive impairment. The aim of this pilot study was to assess the feasibility of long-term adherence to a dietary intervention designed to decrease intake and exposure to circulating AGEs among older adults with type 2 diabetes. Methods: Herein, 75 participants were randomized to either a standard of care (SOC) control arm or to an intervention arm receiving instruction on reducing dietary AGEs intake. The primary outcome was a change in serum AGEs at the end of the intervention. Secondary and exploratory outcomes included adherence to diet and its association with circulating AGEs. Cognitive function and brain imaging were also assessed but were out of the scope of this article (ClinicalTrials.gov Identifier: NCT02739971). Results: The intervention resulted in a significant change over time in several serum AGEs compared to the SOC guidelines. Very high adherence (above 80%) to the AGE-lowering diet was associated with a greater reduction in serum AGEs levels. There were no significant differences between the two arms in any other metabolic markers. Conclusions: A long-term dietary intervention to reduce circulating AGEs is feasible in older adults with type 2 diabetes, especially in those who are highly adherent to the AGE-lowering diet.

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