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 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.

Receptor for advanced glycation end products: a key molecule in the genesis of chronic kidney disease vascular calcification and a potential modulator of sodium phosphate co-transporter PIT-1 expression

2019 ◽  
Vol 34 (12) ◽  
pp. 2018-2030 ◽  
Author(s):  
Karim Belmokhtar ◽  
Jeremy Ortillon ◽  
Stéphane Jaisson ◽  
Ziad A Massy ◽  
Camille Boulagnon Rombi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Advanced Glycation End Products ◽  
Mrna Levels ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
High Phosphate

Abstract Background Chronic kidney disease (CKD) is associated with increased cardiovascular mortality, frequent vascular calcification (VC) and accumulation of uraemic toxins. Advanced glycation end products and S100 proteins interact with the receptor for advanced glycation end products (RAGE). In the present work, we aimed to investigate the role(s) of RAGE in the CKD–VC process. Methods Apoe−/− or Apoe−/−Ager (RAGE)−/− male mice were assigned to CKD or sham-operated groups. A high-phosphate diet was given to a subgroup of Apoe−/−and Apoe−/−Ager−/− CKD mice. Primary cultures of Ager+/+ and Ager−/− vascular smooth muscle cells (VSMCs) were established and stimulated with either vehicle, inorganic phosphate (Pi) or RAGE ligands (S100A12; 20 µM). Results After 12 weeks of CKD we observed a significant increase in RAGE ligand (AGE and S100 proteins) concentrations in the serum of CKD Apoe−/− mice. Ager messenger RNA (mRNA) levels were 4-fold higher in CKD vessels of Apoe−/− mice. CKD Apoe−/− but not CKD Apoe−/− or Ager−/− mice displayed a marked increase in the VC surface area. Similar trends were found in the high-phosphate diet condition. mRNA levels of Runx2 significantly increased in the Apoe−/− CKD group. In vitro, stimulation of Ager+/+VSMCs with Pi or S100A12 induced mineralization and osteoblast transformation, and this was inhibited by phosphonoformic acid (Pi co-transporters inhibitor) and Ager deletion. In vivo and in vitro RAGE was necessary for regulation of the expression of Pit-1, at least in part through production of reactive oxygen species. Conclusion RAGE, through the modulation of Pit-1 expression, is a key molecule in the genesis of VC.

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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