scholarly journals Hyperactivated RAGE in Comorbidities as a Risk Factor for Severe COVID-19—The Role of RAGE-RAS Crosstalk

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 876
Author(s):  
Sara Chiappalupi ◽  
Laura Salvadori ◽  
Rosario Donato ◽  
Francesca Riuzzi ◽  
Guglielmo Sorci
Keyword(s):  
Gene Polymorphisms ◽  
Renin Angiotensin System ◽  
Molecular Target ◽  
Advanced Glycation ◽  
Angiotensin System ◽  
Major Player ◽  
Glycation End Products ◽  
End Products ◽  
And Oxidative Stress

The receptor for advanced glycation-end products (RAGE) is a multiligand receptor with a role in inflammatory and pulmonary pathologies. Hyperactivation of RAGE by its ligands has been reported to sustain inflammation and oxidative stress in common comorbidities of severe COVID-19. RAGE is essential to the deleterious effects of the renin–angiotensin system (RAS), which participates in infection and multiorgan injury in COVID-19 patients. Thus, RAGE might be a major player in severe COVID-19, and appears to be a useful therapeutic molecular target in infections by SARS-CoV-2. The role of RAGE gene polymorphisms in predisposing patients to severe COVID-19 is discussed. 

Role of Advanced Glycation End Products (AGEs) and Oxidative Stress in Diabetic Retinopathy

2008 ◽  
Vol 14 (10) ◽  
pp. 962-968 ◽  
Author(s):  
Sho-ichi Yamagishi ◽  
Seiji Ueda ◽  
Takanori Matsui ◽  
Kazuo Nakamura ◽  
Seiya Okuda
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Oxidative Stress

scholarly journals Hydroxytyrosol Selectively Affects Non-Enzymatic Glycation in Human Insulin and Protects by AGEs Cytotoxicity

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1127
Author(s):  
Ivana Sirangelo ◽  
Margherita Borriello ◽  
Maria Liccardo ◽  
Marika Scafuro ◽  
Paola Russo ◽  
...  
Keyword(s):  
Human Insulin ◽  
Neurodegenerative Disorders ◽  
Cell Biology ◽  
Protein Glycation ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Oxidative Stress

Hydroxytyrosol (HT), the major phenolic compound in olive oil, is attracting increasing interest for its beneficial properties including a notable antioxidant and anti-inflammatory power. In this study, using a combination of biophysical and cell biology techniques, we have tested the role of HT in the formation of advanced glycation end-products (AGEs). AGEs have a key role in clinical sciences as they have been associated to diabetes, neurodegenerative and cardiovascular diseases. In addition, as the incidence of Alzheimer’s disease (AD) is strongly increased in diabetic patients, AGE formation is supposed to be involved in the development of the pathological hallmarks of AD. Our data show that HT selectively inhibits protein glycation reaction in human insulin, and it is able to counteract the AGE-induced cytotoxicity in human neurotypical cells by acting on SIRT1 level and oxidative stress, as well as on inflammatory response. This study identifies new beneficial properties for HT and suggests it might be a promising molecule in protecting against the AGE-induced toxicity, a key mechanism underlying the development and progression of neurodegenerative disorders.

scholarly journals Advanced glycation end-products activate the renin-angiotensin system through the RAGE/PI3-K signaling pathway in podocytes

2012 ◽  
Vol 35 (5) ◽  
pp. 282 ◽  
Author(s):  
Cailan L. Cheng ◽  
Ying Tang ◽  
Zhenda Zheng ◽  
Xun Liu ◽  
Zengchun C. Ye ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Western Blot ◽  
Advanced Glycation End Products ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Advanced Glycation ◽  
Angiotensin System ◽  
Glycation End Products ◽  
End Products ◽  
Ace Activity

Purpose: The purpose of this study was to investigate the effects of advanced glycation end-products (AGEs) on the components of the renin-angiotensin system (RAS) in podocytes and to understand the mechanism of these effects. Methods: Immortalized mouse podocytes were exposed to various concentrations of AGEs for different time intervals. The expression levels of angiotensinogen (AGT), angiotensin II type 1 and 2 receptors (AT1R and AT2R) and renin were examined by real-time PCR and western blot; the receptor for AGEs (RAGE) and both Akt and phosphorylated Akt were examined by western blot; levels of angiotensin II (Ang II) were assayed by ELISA, and the activity of angiotensin-converting enzyme (ACE) was evaluated by measuring the production of hippuric acid in vitro. Results: Treatment with AGEs resulted in significant increases in the expression of AGT (62%, P=0.002) and AT1R (59%, P=0.01). Moreover, Ang II levels increased significantly in both cell lysates (70%, P=0.018) and conditioned media (65%, P=0.01). ACE activity was also significantly higher in cell lysates (68% , P= 0.035) and conditioned media (65%, P=0.023). There were no changes in renin or AT2R expression (P > 0.05). AGEs did increase the expression of RAGE by 50% (P=0.012) and the phosphorylation of Akt by 100% (P=0.001). When podocytes were pretreated with anti-RAGE antibody (50 µg/ml) or the phosphoinositide 3-kinase (PI3-K) inhibitor, LY294002 (10 µM), the AGEs-induced increases in AGT and AT1R expression were reduced. Likewise, Ang II levels and ACE activity decreased significantly. Conclusion: AGEs activate the RAS in podocytes through the RAGE-PI3-K/Akt-dependent pathway and lead to an increase in podocyte apoptosis.

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