F.53. The Receptor for Advanced Glycation End Products (RAGE)Regulates Nuclear Transcription Factor κB (NF-κB) Activation

2009 ◽  
Vol 131 ◽  
pp. S108
Author(s):  
Daolin Tang ◽  
Rui Kang ◽  
Tara Loux ◽  
Chun-Wei Cheh ◽  
Herbert Zeh ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Nuclear Transcription Factor ◽  
Glycation End Products ◽  
End Products

scholarly journals A Systematic Study of Mechanism of Sargentodoxa cuneata and Patrinia scabiosifolia Against Pelvic Inflammatory Disease With Dampness-Heat Stasis Syndrome via Network Pharmacology Approach

2020 ◽  
Vol 11 ◽  
Author(s):  
Luanqian Hu ◽  
Yuqi Chen ◽  
Tingting Chen ◽  
Dan Huang ◽  
Shihua Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Pelvic Inflammatory Disease ◽  
Advanced Glycation End Products ◽  
Inflammatory Disease ◽  
Experimental Validation ◽  
Advanced Glycation ◽  
Nuclear Transcription Factor ◽  
Tnf Α ◽  
Glycation End Products ◽  
End Products

Objective: To investigate the mechanism of Sargentodoxa cuneata (Oliv.) Rehder & E.H.Wilson (SC) and Patrinia scabiosifolia (PS) against Pelvic Inflammatory Disease with Dampness-Heat Stasis Syndrome via network pharmacological approach and experimental validation.Methods: The active compounds with OB ≥ 30% and DL ≥ 0.18 were obtained from TCMSP database and further confirmed by literature research. The targets of the compounds and disease were acquired from multiple databases, such as GeneCards, CTD and TCMSP database. The intersection targets were identified by Venny software. Cytoscape 3.7.0 was employed to construct the protein-protein interaction (PPI) network and compound-target network. Moreover, GO enrichment and KEGG pathway analysis were analyzed by DAVID database. Finally, CCK-8, Griess assay and a cytometric bead array (CBA) immunoassay were used for experimental validation by detecting the influence of the active compounds on proliferation of macrophage, release of NO and TNF-α after LPS treatment.Results: 9 bioactive compounds were identified from SC and PS. Those compounds corresponded to 134 targets of pelvic inflammatory disease with dampness-heat stasis syndrome. The targets include vascular endothelial growth factor A (VEGFA), von willebrand factor (VWF), interleukin 6 (IL6), tumor necrosis factor (TNF) and nuclear transcription factor 1 (NFκB1). They act on the signaling pathways like advanced glycation end products-receptor of advanced glycation end products (AGE-RAGE), focal adhesion (FA), Toll-like receptor (TLR) and nuclear transcription factor κB (NF-κB). In addition, by in vitro validation, the selected active components of SC and PS such as acacetin, kaempferol, linarin, isovitexin, sinoacutine could significantly inhibit the release of NO induced by LPS, respectively. Moreover, different dose of acacetin, kaempferol, isovitexin and sinoacutine significantly inhibits the TNF-α production.Conclusion: This study provides solid evidence for the anti-inflammatory mechanism of SC and PS against pelvic inflammatory disease with dampness-heat stasis syndrome, which will provide a preliminary evidence and novelty ideas for future research on the two herbs.

Impaired transcription factor interplay in addition to advanced glycation end products suppress podocalyxin expression in high glucose-treated human podocytes

2009 ◽  
Vol 297 (3) ◽  
pp. F594-F603 ◽  
Author(s):  
Garyfalia I. Drossopoulou ◽  
Nikolaos E. Tsotakos ◽  
Effie C. Tsilibary
Keyword(s):  
Transcription Factor ◽  
Advanced Glycation End Products ◽  
Wilms Tumor ◽  
Mrna Levels ◽  
Advanced Glycation ◽  
Protein Levels ◽  
Glucose Levels ◽  
Glycation End Products ◽  
End Products

Podocalyxin represents a Wilms’ tumor suppressor protein (WT1)-regulated differentiation marker for glomerular epithelium. We provide evidence concerning mechanisms involved in the regulation of podocalyxin expression following long-term exposure to increased (25 mM) glucose levels. Prolonged culture of conditionally immortalized human podocytes in 25 mM glucose induced suppression of podocalyxin expression both at the protein and mRNA levels, whereas WT1 protein levels remained unaltered. WT1 interacted with another transcription factor, CRE-binding protein (CBP). This association was decreased by 40% in the presence of 25 mM glucose. Chromatin immunoprecipitation assays on chromatin from podocytes cultured in 25 mM glucose revealed reduced WT1 binding to podocalyxin promoter sequences, probably resulting from impaired WT1-CBP interactions. We explored the possible role of glucose-induced adducts (advanced glycation end products; AGEs) in impairing interactions between WT1 and CBP, with the use of aminoguanindine, an inhibitor of AGE formation. Podocytes were cultured in the simultaneous presence of 20 mM aminoguanidine and 25 mM glucose, and podocalyxin protein levels were examined. Aminoguanidine effectively prevented downregulation of podocalyxin protein levels but could not restore podocalyxin levels once expression was suppressed. Thus increased glucose apparently impaired the ability of WT1 to initiate transcription in part by decreased association of WT1 with CBP. Administration of aminoguanidine concomitant with increasing glucose levels in our in vitro model system protected from glucose-induced “silencing” of the podocalyxin gene, suggesting that AGEs play an important role in suppressing its expression in diabetic conditions.

Advanced glycation end products induce apoptosis in fibroblasts through activation of ROS, MAP kinases, and the FOXO1 transcription factor

2007 ◽  
Vol 292 (2) ◽  
pp. C850-C856 ◽  
Author(s):  
Mani Alikhani ◽  
Christine M. MacLellan ◽  
Markos Raptis ◽  
Siddarth Vora ◽  
Philip C. Trackman ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Advanced Glycation End Products ◽  
Map Kinases ◽  
Caspase 3 ◽  
Fold Increase ◽  
Advanced Glycation ◽  
Kinase Activation ◽  
Glycation End Products ◽  
End Products ◽  
Induced Apoptosis

Advanced glycation end products (AGEs) are elevated in aged and diabetic individuals and are associated with pathological changes associated with both. Previously we demonstrated that the AGE Nε-(carboxymethyl)lysine (CML)-collagen induced fibroblast apoptosis through the cytoplasmic and mitochondrial pathways and the global induction of proapoptotic genes. In the present study we investigated upstream mechanisms of CML-collagen-induced apoptosis. CML-collagen induced activation of the proapoptotic transcription factor FOXO1 compared with unmodified collagen. When FOXO1 was silenced, CML-collagen-stimulated apoptosis was reduced by ∼75% compared with fibroblasts incubated with nonsilencing small interfering RNA, demonstrating the functional significance of FOXO1 activation ( P < 0.05). CML-collagen but not control collagen also induced a 3.3-fold increase in p38 and a 5.6-fold increase in JNK(1/2) activity ( P < 0.05). With the use of specific inhibitors, activation of p38 and JNK was shown to play an important role in CML-collagen-induced activation of FOXO1 and caspase-3. Moreover, inhibition of p38 and JNK reduced CML-collagen-stimulated apoptosis by 48 and 57%, respectively, and by 89% when used together ( P < 0.05). In contrast, inhibition of the phosphatidylinositol 3-kinase/Akt pathway enhanced FOXO1 activation. p38 and JNK stimulation by CML-collagen was almost entirely blocked when formation of ROS was inhibited and was partially reduced by NO and ceramide inhibitors. These inhibitors also reduced apoptosis to a similar extent. Together these data support a model in which AGE-induced apoptosis involves the formation of ROS, NO, and ceramide and leads to p38 and JNK MAP kinase activation, which in turn induces FOXO1 and caspase-3.

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