scholarly journals Autophagy Inhibits the Accumulation of Advanced Glycation End Products by Promoting Lysosomal Biogenesis and Function in the Kidney Proximal Tubules

Diabetes ◽  
2017 ◽  
Vol 66 (5) ◽  
pp. 1359-1372 ◽  
Author(s):  
Atsushi Takahashi ◽  
Yoshitsugu Takabatake ◽  
Tomonori Kimura ◽  
Ikuko Maejima ◽  
Tomoko Namba ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Proximal Tubules ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Function ◽  
Kidney Proximal Tubules

scholarly journals The Modern Western Diet Rich in Advanced Glycation End-Products (AGEs): An Overview of Its Impact on Obesity and Early Progression of Renal Pathology

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1748 ◽  
Author(s):  
Arianna Bettiga ◽  
Francesco Fiorio ◽  
Federico Di Marco ◽  
Francesco Trevisani ◽  
Annalisa Romani ◽  
...  
Keyword(s):  
Chronic Diseases ◽  
Advanced Glycation End Products ◽  
Cell Function ◽  
Advanced Glycation ◽  
Covalent Bonds ◽  
Physiological Processes ◽  
Glycation End Products ◽  
End Products ◽  
And Function

Advanced glycation end-products (AGEs) are an assorted group of molecules formed through covalent bonds between a reduced sugar and a free amino group of proteins, lipids, and nucleic acids. Glycation alters their structure and function, leading to impaired cell function. They can be originated by physiological processes, when not counterbalanced by detoxification mechanisms, or derive from exogenous sources such as food, cigarette smoke, and air pollution. Their accumulation increases inflammation and oxidative stress through the activation of various mechanisms mainly triggered by binding to their receptors (RAGE). So far, the pathogenic role of AGEs has been evidenced in inflammatory and chronic diseases such as chronic kidney disease, cardiovascular disease, and diabetic nephropathy. This review focuses on the AGE-induced kidney damage, by describing the molecular players involved and investigating its link to the excess of body weight and visceral fat, hallmarks of obesity. Research regarding interventions to reduce AGE accumulation has been of great interest and a nutraceutical approach that would help fighting chronic diseases could be a very useful tool for patients’ everyday lives.

Advanced Glycation End Products Modulate the Maturation and Function of Peripheral Blood Dendritic Cells

Diabetes ◽  
2004 ◽  
Vol 53 (6) ◽  
pp. 1452-1458 ◽  
Author(s):  
C. L. Price ◽  
P. S. Sharp ◽  
M. E. North ◽  
S. J. Rainbow ◽  
S. C. Knight
Keyword(s):  
Dendritic Cells ◽  
Advanced Glycation End Products ◽  
Peripheral Blood ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Function

Expression and Function of Receptors for Advanced Glycation End Products in Bovine Corneal Endothelial Cells

2003 ◽  
Vol 44 (2) ◽  
pp. 521 ◽  
Author(s):  
Yuichi Kaji ◽  
Shiro Amano ◽  
Tomohiko Usui ◽  
Tetsuro Oshika ◽  
Kenji Yamashiro ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Advanced Glycation End Products ◽  
Corneal Endothelial Cells ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Function

scholarly journals Impact of intracellular toxic advanced glycation end-products (TAGE) on murine myoblast cell death:A non-clinical study

2020 ◽  
Author(s):  
Takanobu Takata ◽  
Akiko Sakasai-Sakai ◽  
Masayoshi Takeuchi
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Advanced Glycation End Products ◽  
C2c12 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Myoblast Cell ◽  
And Function

Abstract Background: Sarcopenia is a progressive condition that is characterized by decreases in skeletal muscle mass and function. Although sarcopenia is associated with lifestyle-related diseases (LSRD), the mechanisms underlying cell death in myoblasts, which differentiate to myotubes, remain unclear. We previously designated glyceraldehyde (an intermediate of glucose/fructose metabolism)-derived advanced glycation end-products (AGEs) as toxic AGEs (TAGE) because of their cytotoxicity and involvement in LSRD, and hypothesized that TAGE contribute to cell death in myoblasts. Methods: C2C12 cells, which are murine myoblasts, were treated with 0, 0.5, 1, 1.5, and 2 mM glyceraldehyde for 24 h. Cell viability and intracellular TAGE were then assessed using 5-[2,4,-bis(sodioxysulfonyl)phenyl]-3-(2-methoxy-4-nitrophenyl)-2-(4-nitrophenyl)-2H-tetrazole-3-ium (WST-8) and slot blot assays. Cells were pretreated with 8 mM aminoguanidine , an inhibitor of AGE production, for 2 h, followed by 0, 1.5, and 2 mM glyceraldehyde for 24 h. Cell viability and intracellular TAGE levels were then assessed. Serum TAGE levels in STAM mice, in which there were four stages (no steatosis, simple steatosis, steatohepatitis, and fibrosis), were measured using a competitive enzyme-linked immunosorbent assay. Results were expressed as TAGE units (U) per milliliter of serum, with 1 U corresponding to 1.0 μg of glyceraldehyde-derived AGE-bovine serum albumin (BSA) (TAGE-BSA). The viability of cells treated with 20, 50, and 100 μg/mL non-glycated BSA and TAGE-BSA for 24 h was assessed using the WST-8 assay. Results: In C2C12 cells treated with 1.5 and 2 mM glyceraldehyde, cell viability decreased to 47.7% ( p =0.0021) and 5.0% ( p =0.0001) and intracellular TAGE levels increased to 6.0 and 15.9 μg/mg protein, respectively. Changes in cell viability and TAGE production were completely inhibited by 8 mM aminoguanidine. Serum TAGE levels at the steatohepatitis and fibrosis stages were 10.51 ±1.16 and 10.44±0.95 U/mL, respectively, and were higher than those at the no steatosis stage ( 7.27 ±0.18 U/mL). Cell death was not induced by 20 or 50 μg/mL TAGE-BSA. The viabilities of C2C12 cells treated with 100 μg/mL non-glycated BSA and TAGE-BSA were 105.0% ( p =0.2890) and 85.3% ( p =0.0217), respectively. Conclusion: Intracellular TAGE strongly induced cell death in C2C12 cells and may also induce myoblast cell death in LSRD model mice.

scholarly journals Placental Morphology and Cellular Characteristics in Stillbirths in Women With Diabetes and Unexplained Stillbirths

2020 ◽  
Vol 145 (1) ◽  
pp. 82-89
Author(s):  
Alan Kerby ◽  
Daniel Shingleton ◽  
Gauri Batra ◽  
Megan C. Sharps ◽  
Bernadette C. Baker ◽  
...  
Keyword(s):  
T Cells ◽  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Phenotypic Differences ◽  
Live Births ◽  
Glycation End Products ◽  
End Products ◽  
Hofbauer Cells ◽  
Placental Macrophages ◽  
And Function

Context.— Women with diabetes have increased stillbirth risk. Although the underlying pathophysiological processes are poorly understood, stillbirth is frequently related to abnormal placental structure and function. Objective.— To investigate placental morphology and cellular characteristics in the placentas of women with diabetes who had stillbirths and stillbirths of unexplained cause. Design.— Placentas from women with uncomplicated live births, live births in women with diabetes, unexplained stillbirths, and stillbirths related to diabetes (n = 10/group) underwent clinical histopathologic assessment and were also investigated using immunohistochemical staining to quantify syncytial nuclear aggregates, proliferation, trophoblast area, vascularization, T cells, placental macrophages (Hofbauer cells), and the receptor for advanced glycation end products. Results.— Ki67+ cells were decreased in unexplained stillbirths compared with live births in women with diabetes. Both stillbirth groups had increased cytokeratin 7+/nuclear area compared with controls. Blood vessels/villi were decreased in unexplained stillbirth compared with live births from women with diabetes. Compared with uncomplicated controls, CD163+ macrophages were increased in live births in women with diabetes and unexplained stillbirths, and further increased in stillbirths related to diabetes. There was no change in CD3+ T cells or syncytial nuclear aggregates. Receptor for advanced glycation end products–positive cells were decreased in both stillbirth groups compared with diabetes-related live births. Co-localization of receptor for advanced glycation end products in macrophages was increased in both stillbirth groups compared with live birth groups. Conclusions.— Stillbirths related to diabetes exhibit placental phenotypic differences compared with live births. Further investigation of these parameters may provide understanding of the pathologic mechanisms of stillbirth and aid the development of stillbirth prevention strategies.

scholarly journals Involvement of Advanced Glycation End Products in the Pathogenesis of Diabetic Retinopathy

2018 ◽  
Vol 48 (2) ◽  
pp. 705-717 ◽  
Author(s):  
Jing Xu ◽  
Lin-Jiang Chen ◽  
Jian Yu ◽  
Han-Jing Wang ◽  
Fan Zhang ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Advanced Glycation End Products ◽  
Intracellular Signaling ◽  
Vascular Inflammation ◽  
Advanced Glycation ◽  
Blood Retinal Barrier ◽  
Glycation End Products ◽  
End Products ◽  
And Function ◽  
Medical Burden

Diabetic retinopathy (DR) is a common and devastating microvascular complication of diabetes and a major cause of acquired blindness in young adults. Advanced glycation end products (AGEs) accumulated under hyperglycemic conditions are thought to play an important role in the pathogenesis of DR. AGEs can exert their deleterious effects by acting directly to induce aberrant crosslinking of extracellular matrix proteins, to increase vascular stiffness, altering vascular structure and function. Moreover, AGEs binding to the receptor for AGEs (RAGE) evokes intensive intracellular signaling cascades that leading to endothelial dysfunction, elaboration of key proinflammatory cytokines and proangiogenic factors, mediating pericyte apoptosis, vascular inflammation and angiogenesis, as well as breakdown of the inner blood-retinal barrier (BRB), the end result of all these events is damage to the neural and vascular components of the retina. Elucidation of AGE-induced mechanisms will help in the understanding of the complex cellular and molecular pathogenesis associated with DR. Novel anti-AGEs agents or AGE crosslink “breakers” are being investigated, it is hoped that in next few years, some of these promising therapies will be successfully applied in clinical context, aiming to reduce the major economical and medical burden caused by DR.

scholarly journals Mapping protein carboxymethylation sites provides insights into their role in proteostasis and cell proliferation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Simone Di Sanzo ◽  
Katrin Spengler ◽  
Anja Leheis ◽  
Joanna M. Kirkpatrick ◽  
Theresa L. Rändler ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Specific Protein ◽  
Protein Glycation ◽  
Advanced Glycation ◽  
Protein Targets ◽  
Glycation End Products ◽  
End Products ◽  
Functional Consequences ◽  
Cell Cycle Perturbation ◽  
And Function

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

Sign in / Sign up

Export Citation Format

Share Document