Advanced glycation end-products induce heparanase expression in endothelial cells by the receptor for advanced glycation end products and through activation of the FOXO4 transcription factor

2011 ◽  
Vol 354 (1-2) ◽  
pp. 47-55 ◽  
Author(s):  
Xiao-Fei An ◽  
Lei Zhou ◽  
Peng-Jun Jiang ◽  
Ming Yan ◽  
Yu-Jun Huang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

scholarly journals RasGRP2 inhibits glyceraldehyde-derived toxic advanced glycation end-products from inducing permeability in vascular endothelial cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jun-ichi Takino ◽  
Takuma Sato ◽  
Takumi Kanetaka ◽  
Kasumi Okihara ◽  
Kentaro Nagamine ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Permeability ◽  
Advanced Glycation End Products ◽  
Protective Factor ◽  
Vascular Endothelial Cells ◽  
Enzymatic Reaction ◽  
Vascular Endothelial ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

AbstractAdvanced glycation end-products (AGEs) are formed by the non-enzymatic reaction of sugars and proteins. Among the AGEs, glyceraldehyde-derived toxic AGEs (TAGE) are associated with various diseases, including diabetic complications such as diabetic retinopathy (DR). The risk of developing DR is strongly associated with poor glycemic control, which causes AGE accumulation and increases AGE-induced vascular permeability. We previously reported that Ras guanyl nucleotide releasing protein 2 (RasGRP2), which activates small G proteins, may play an essential role in the cell response to toxicity when exposed to various factors. However, it is not known whether RasGRP2 prevents the adverse effects of TAGE in vascular endothelial cells. This study observed that TAGE enhanced vascular permeability by disrupting adherens junctions and tight junctions via complex signaling, such as ROS and non-ROS pathways. In particular, RasGRP2 protected adherens junction disruption, thereby suppressing vascular hyper-permeability. These results indicate that RasGRP2 is an essential protective factor of vascular permeability and may help develop novel therapeutic strategies for AGE-induced DR.

scholarly journals Aqueous Extract of Glucoraphanin-Rich Broccoli Sprouts Inhibits Formation of Advanced Glycation End Products and Attenuates Inflammatory Reactions in Endothelial Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Ami Sotokawauchi ◽  
Yuji Ishibashi ◽  
Takanori Matsui ◽  
Sho-ichi Yamagishi
Keyword(s):  
Endothelial Cells ◽  
Aqueous Extract ◽  
Advanced Glycation End Products ◽  
Ros Generation ◽  
Mrna Levels ◽  
Advanced Glycation ◽  
Broccoli Sprouts ◽  
Glycation End Products ◽  
End Products ◽  
Broccoli Sprout

We have previously shown that sulforaphane not only inhibits formation of advanced glycation end products (AGEs) but also exerts anti-inflammatory effects on AGE-exposed human umbilical vein endothelial cells (HUVECs) and AGE-injected rat aortae. Here we examined the effects of aqueous extract of glucoraphanin-rich broccoli sprouts on formation of AGEs and then investigated whether the extract could attenuate inflammatory or oxidative stress reactions in tumor necrosis factor-alpha (TNF-α)- or AGE-exposed HUVECs. Fresh broccoli sprouts were homogenized in phosphate-buffered saline and filtered through a gauze. After centrifugation, clear extract was obtained. AGE formation was measured by enzyme-linked immunosorbent assay. Gene expression was evaluated by real-time reverse transcription-polymerase chain reaction. Reactive oxygen species (ROS) generation were measured using a fluorescent dye. Five percent broccoli sprout extract inhibited the formation of AGEs, reduced basal gene expressions of monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1,) and receptor for AGEs (RAGE), and upregulated endothelial nitric oxide synthase (eNOS) mRNA levels in HUVECs. TNF-α upregulated MCP-1, ICAM-1, and RAGE mRNA levels in HUVECs, all of which were attenuated by the treatment with 1% broccoli sprout extract. Pretreatment of 1% broccoli sprout extract prevented the ROS generation in HUVECs evoked by AGEs. The present study demonstrates that sulforaphane-rich broccoli sprout extract could inhibit the AGE-RAGE axis and exhibit anti-inflammatory actions in HUVECs. Supplementation of sulforaphane-rich broccoli sprout extract may play a protective role against vascular injury.

scholarly journals Endogenous Secretory Receptor for Advanced Glycation End Products Protects Endothelial Cells from AGEs Induced Apoptosis

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Guomin Yang ◽  
Yinqiong Huang ◽  
Xiaohong Wu ◽  
Xiahong Lin ◽  
Jinting Xu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Advanced Glycation End Products ◽  
Proinflammatory Cytokine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Advanced Glycation ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Glycation End Products ◽  
End Products

Endogenous secretory receptor for advanced glycation end products (esRAGE) binds extracellular RAGE ligands and blocks RAGE activation on the cell surface, protecting endothelial cell function. However, the underlying mechanism remains unclear. Endothelial cells overexpressing the esRAGE gene were generated using a lentiviral vector. Then, quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to assess esRAGE mRNA and protein levels, respectively. Hoechst-PI double staining was used to assess apoptosis. Western blot and qRT-PCR were used to assess the expression levels of apoptosis-related factors and the proinflammatory cytokine NF-кB. Compared with the control group, AGEs significantly induced endothelial cell apoptosis, which was significantly reduced by esRAGE overexpression. Incubation with AGEs upregulated the proapoptotic factor Bax and downregulated the antiapoptotic factor Bcl-2. Overexpression of esRAGE reduced Bax expression induced by AGEs and increased Bcl-2 levels. Furthermore, AGEs increased the expression levels of proinflammatory cytokine NF-кB, which were reduced after esRAGE overexpression. esRAGE protects endothelial cells from AGEs associated apoptosis, by downregulating proapoptotic (Bax) and inflammatory (NF-кB) factors and upregulating the antiapoptotic factor Bcl-2.

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