Inhibition of RAGE Axis Signaling: A Pharmacological Challenge

2019 ◽  
Vol 20 (3) ◽  
pp. 340-346 ◽  
Author(s):  
Armando Rojas ◽  
Miguel Morales ◽  
Ileana Gonzalez ◽  
Paulina Araya
Keyword(s):  
Cell Surface Receptor ◽  
Clinical Settings ◽  
Advanced Glycation ◽  
Binding Domains ◽  
Pharmacological Challenge ◽  
Glycation End Products ◽  
End Products ◽  
Attractive Therapeutic Target ◽  
Surface Receptor ◽  
Recognition Receptor

The Receptor for Advanced Glycation End Products (RAGE) is an important cell surface receptor, which belongs to the IgG super family and is now considered as a pattern recognition receptor. Because of its relevance in many human clinical settings, it is now pursued as a very attractive therapeutic target. However, particular features of this receptor such as a wide repertoire of ligands with different binding domains, the existence of many RAGE variants as well as the presence of cytoplasmatic adaptors leading a diverse signaling, are important limitations in the search for successful pharmacological approaches to inhibit RAGE signaling. Therefore, the present review aimed to display the most promising approaches to inhibit RAGE signaling, and provide an up to date review of progress in this area.

Pathological Role of Advanced Glycation End Products (AGEs) and their Receptor Axis in Atrial Fibrillation

2019 ◽  
Vol 19 (13) ◽  
pp. 1040-1048 ◽  
Author(s):  
Sho-ichi Yamagishi ◽  
Ami Sotokawauchi ◽  
Takanori Matsui
Keyword(s):  
Atrial Fibrillation ◽  
Advanced Glycation End Products ◽  
Tertiary Structure ◽  
Cell Surface Receptor ◽  
Advanced Glycation ◽  
Chronic Hyperglycemia ◽  
Glycation End Products ◽  
End Products ◽  
Surface Receptor

Accumulating evidence has shown that the incidence of atrial fibrillation (AF) is higher in patients with diabetes, especially those with poor glycemic control or long disease duration. Nonenzymatic glycation of amino acids of proteins, lipids, and nucleic acids has progressed under normal aging process and/or diabetic condition, which could lead to the formation and accumulation of advanced glycation end products (AGEs). AGEs not only alter the tertiary structure and physiological function of macromolecules, but also evoke inflammatory and fibrotic reactions through the interaction of cell surface receptor for AGEs (RAGE), thereby being involved in aging-related disorders. In this paper, we briefly review the association of chronic hyperglycemia and type 1 diabetes with the risk of AF and then discuss the pathological role of AGE-RAGE axis in AF and its thromboembolic complications.

scholarly journals Serum levels of 1,5-anhydroglucitol and 1,5-anhydrofructose-derived advanced glycation end products in patients undergoing hemodialysis

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Kenji Tanaka ◽  
Akiko Sakasai-Sakai ◽  
Yasuki Motomiya ◽  
Tatsuo Yoneda ◽  
Masayoshi Takeuchi
Keyword(s):  
Advanced Glycation End Products ◽  
Serum Levels ◽  
Underlying Mechanism ◽  
Clinical Settings ◽  
Renal Tubules ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Patient Groups ◽  
Regular Hemodialysis

Abstract Background 1,5-anhydroglucitol is a reduction product of 1,5-anhydrofructose. Circulating 1,5-anhydroglucitol is usually excreted by the kidneys and is reabsorbed via sodium-glucose co-transporter 4 in the renal tubules. In patients on hemodialysis, serum levels of 1,5-anhydroglucitol have been reported to be low; however, the underlying mechanism remains unclear. Methods We measured inter-dialysis changes in the levels of serum 1,5-anhydroglucitol and 1,5-anhydrofructose-derived advanced glycation end products (AGEs) in 78 patients on hemodialysis. Serum levels of 1,5-anhydrofructose-derived AGEs were also determined using a polyclonal antibody. Results The serum 1,5-anhydroglucitol level was decreased to as low as 2.0 μg/mL in the regular hemodialysis group; however, we could not verify changes in the serum 1,5-anhydroglucitol level during inter-dialysis days because of undetectable levels in 29 patients. The measured serum level of 1,5-anhydrofructose-derived AGEs was significantly increased in both patient groups. In addition, the 1,5-anhydrofructose-derived AGEs/1,5-anhydroglucitol ratio was higher in patients on hemodialysis than in controls. Conclusions Accelerated glycation of 1,5-anhydrofructose is one possible mechanism by which serum 1,5-anhydroglucitol levels are lowered in patients on HD, and we propose that the 1,5-anhydrofructose-derived AGEs/1,5-anhydroglucitol ratio should be measured in clinical settings in which patients have low serum levels of 1,5-AG.

scholarly journals Association of the receptor for advanced glycation end-products (RAGE) gene polymorphisms in Malaysian patients with chronic kidney disease

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1908 ◽  
Author(s):  
Foo Nian Wong ◽  
Kek Heng Chua ◽  
Umah Rani Kuppusamy ◽  
Chew Ming Wong ◽  
Soo Kun Lim ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Advanced Glycation End Products ◽  
Cell Surface Receptor ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Advanced Glycation ◽  
Malaysian Population ◽  
Glycation End Products ◽  
End Products

Background:Chronic kidney disease (CKD) is a condition associated with progressive loss of kidney function and kidney damage. The two common causes of CKD are diabetes mellitus and hypertension. Other causes of CKD also include polycystic kidney disease, obstructive uropathy and primary glomerulonephritis. The receptor for advanced glycation end-products (RAGE) is a multi-ligand cell surface receptor of the immunoglobulin superfamily and it has been associated with kidney disease in both non-diabetic and diabetic patients. Presently, data on the association between RAGE polymorphisms and CKD in the Malaysian population is limited, while numerous studies have reported associations of RAGE polymorphisms with diabetic complications in other populations. The present study aims to explore the possibility of using RAGE polymorphisms as candidate markers of CKD in Malaysian population by using association analysis.Methods:A total of 102 non-diabetic CKD patients, 204 diabetic CKD patients and 345 healthy controls were enrolled in the study. DNA isolated from blood samples were subjected to genotyping of RAGE G82S, −374T/A, −429T/C, 1704G/T and 2184A/G polymorphisms using real-time polymerase chain reaction (PCR). The 63-bp deletion, a polymorphism in the RAGE gene promoter, was genotyped using conventional PCR method and visualized using agarose gel electrophoresis. The collective frequencies of genotypes with at least one copy of the minor alleles of the four polymorphisms were compared between the non-diabetic CKD patients, diabetic CKD patients and healthy controls.Results:After adjustment of age, gender and ethnic groups in binary logistic regression analysis, the G82S CT + TT genotypes were associated with non-diabetic CKD patients when compared with diabetic CKD patients (p= 0.015, OR = 1.896, 95% CI = 1.132–3.176). After further adjustment of CKD comorbidities, the G82S CT + TT genotypes were still associated with non-diabetic CKD patients when compared with diabetic CKD patients (p= 0.011, OR = 2.024, 95% CI = 1.178–3.476). However, it cannot be suggested that G82S polymorphism was associated with CKD in non-diabetic patients in this study. This is because there were no significant differences in the frequencies of G82S CT + TT genotypes between non-diabetic CKD patients and healthy controls. In addition, the RAGE −374T/A, −429T/C, 1704G/T, 2184A/G and 63-bp deletion polymorphisms were also not associated with non-diabetic CKD patients and diabetic CKD patients in this study.Conclusion:The G82S, −374T/A, −429T/C, 1704G/T, 2184A/G and 63-bp deletion polymorphisms examined in this study were not associated with chronic kidney disease in the Malaysian patients.

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