Role of advanced glycation end products in cellular signaling

Ott, Christiane; Jacobs, Kathleen; Haucke, Elisa; Santos, Anne Navarrete; Grune, Tilman; Simm, Andreas

doi:10.1016/j.redox.2013.12.016

Cited by 957 publications

(854 citation statements)

References 223 publications

(203 reference statements)

Supporting

Mentioning

817

Contrasting

Unclassified

Order By: Relevance

“…reported to stimulate various signaling cascades involving MAPKs, such as ERK-1/2, JNK, and p38 (Ott et al 2014). However, in the present study, RAGE deletion markedly inhibited the phosphorylation of ERK, but not JNK or p38, in HUVECs, suggesting that the induction of pro-inflammatory cytokine expression by glycol-AGEs may be ERK-dependent (Figure 2).…”

Section: Discussioncontrasting

confidence: 66%

Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium

Nam

Son

Lee

et al. 2015

Cell Communication & Adhesion

View full text Add to dashboard Cite

Advanced glycation end-products (AGEs) are involved in the development of vascular smooth muscle cell (VSMC) dysfunction and the progression of atherosclerosis. However, AGEs may indirectly affect VSMCs via AGEs-induced signal transduction between monocytes and human umbilical endothelial cells (HUVECs), rather than having a direct influence. This study was designed to elucidate the signaling pathway underlying AGEs-RAGE axis influence on VSMC dysfunction using a co-culture system with monocytes, HUVECs and VSMCs. AGEs stimulated production of reactive oxygen species and pro-inflammatory mediators such as tumor necrosis factor-a and interleukin1b via extracellular-signal-regulated kinases phosphorylation and nuclear factor-jB activation in HUVECs. It was observed that AGEs-induced pro-inflammatory cytokines increase VSMC proliferation, inflammation and vascular remodeling in the co-culture system. This result implies that RAGE plays a role in AGEs-induced VSMC dysfunction. We suggest that the regulation of signal transduction via the AGEs-RAGE axis in the endothelium can be a therapeutic target for preventing atherosclerosis.ARTICLE HISTORY

show abstract

Section: Discussioncontrasting

confidence: 66%

Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium

Nam

Son

Lee

et al. 2015

Cell Communication & Adhesion

View full text Add to dashboard Cite

show abstract

“…Aging-associated diseases such as cardiovascular disease, neurodegenerative disorders and other chronic conditions play important roles in restraining the quality of life of the aging population (Rahman 2007, Ott et al 2014. A lot of chronic diseases are associated with the accumulation of age-related modified biomolecules.…”

Section: Introductionmentioning

confidence: 99%

“…A lot of chronic diseases are associated with the accumulation of age-related modified biomolecules. In the context of cardiovascular diseases, the accumulation of damaged biomolecules is responsible for the atherosclerotic plaque formation and contributes to the endothelial dysfunction (Negre-Salvayre et al 2008, Ott et al 2014.…”

Section: Introductionmentioning

confidence: 99%

Key structural and functional differences between early and advanced glycation products

Paradela-Dobarro

Rodiño-Janeiro

Alonso

et al. 2016

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Most of the studies on advanced glycation end products (AGE) have been carried out with uncharacterized mixtures of AGE, so the observed effects cannot be linked to defined structures. Therefore, we analysed the structural differences between glycated human serum albumin (gHSA), a low glycated protein, and AGE-human serum albumin (AGE-HSA), a high glycated protein, and we compared their effects on endothelial functionality. Specifically, we characterized glycation and composition on both early and advanced stage glycation products of gHSA and AGE-HSA by using the MALDI-TOF-mass spectrometry assay. Furthermore, we studied the effects of both types of glycation products on reactive oxygen species (ROS) production and in the expression of vascular and intercellular cell adhesion molecules (VCAM-1 and ICAM-1) on human umbilical endothelial cells (HUVEC). We also measured the adhesion of peripheral blood mononuclear cells (PBMC) to HUVEC. Low concentrations of gHSA enhanced long-lasting ROS production in HUVEC, whereas lower concentrations of AGE-HSA caused the anticipation of the induced extracellular ROS production. Both gHSA and AGE-HSA up-regulated the expression of VCAM-1 and ICAM-1 at mRNA levels. Nevertheless, only AGE-HSA increased protein levels and enhanced the adhesion of PBMC to HUVEC monolayers. Functional differences were observed between gHSA and AGE-HSA, causing the latter an anticipation of the pro-oxidant effects in comparison to gHSA. Moreover, although both molecules induced genetic up-regulation of adhesion molecules in HUVEC, only the high glycated protein functionally increased mononuclear cell adhesion to endothelial monolayers. These observations could have important clinical consequences in the development of diabetic vascular complications.

show abstract

“…RAGE consists of one cytoplasmic domain at the C terminus, one transmembrane domain, two distinct constant domains (C1 and C2), and one variable domain at the N terminus (V) (17). The variable domain is predominantly related to ligand binding, such as that seen in most S100 family proteins (18), advanced glycation end products (19,20), amyloid-␤ protein (21), and amphoterin (HMGB1 (high mobility group protein 1)) (22, 23). Some ligands can interact with both the variable domain and constant domain simultaneously, such as S100B (24) and S100A12 protein (25,26).…”

mentioning

confidence: 99%

Tranilast Blocks the Interaction between the Protein S100A11 and Receptor for Advanced Glycation End Products (RAGE) V Domain and Inhibits Cell Proliferation

Huang

Chou

2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

The human S100 calcium-binding protein A11 (S100A11) is a member of the S100 protein family. Once S100A11 proteins bind to calcium ions at EF-hand motifs, S100A11 changes its conformation, promoting interaction with target proteins. The receptor for advanced glycation end products (RAGE) consists of three extracellular domains, including the V domain, C1 domain, and C2 domain. In this case, the V domain is the target for mutant S100A11 (mS100A11) binding. RAGE binds to the ligands, resulting in cell proliferation, cell growth, and several signal transduction cascades. We used NMR and fluorescence spectroscopy to demonstrate the interactions between mS100A11 and RAGE V domain. The tranilast molecule is a drug used for treating allergic disorders. We discovered that the RAGE V domain and tranilast would interact with mS100A11 by using 1 H-15 N HSQC NMR titrations. According to the results, we obtained two binary complex models from the HADDOCK program, S100A11-RAGE V domain and S100A11-tranilast, respectively. We overlapped two binary complex models with the same orientation of S100A11 homodimer and demonstrated that tranilast would block the binding site between S100A11 and the RAGE V domain. We further utilized a water-soluble tetrazolium-1 assay to confirm this result. We think that the results will be potentially useful in the development of new anti-cancer drugs.Human S100 proteins are a family of low molecular weight, homodimeric, and acidic proteins that contain two EF-hand motifs that can bind to calcium ions (1, 2). Human S100A11 (S100C) protein is a member of the S100 family. S100A11 was first discovered in chicken gizzards and is also called calgizzarin (3). S100A11 protein can be expressed in the heart, kidney, liver, lung, and other tissues. It is most abundant in smooth muscle tissues (4). In previous studies, it has been shown that S100A11 protein can interact with various other proteins, such as annexin A1 and A2, ATPase Rad54B, and RAGE.2 The interactions induce activities or conformational changes of these target proteins and further promote the specific physiological functions. Calcium-bound S100A11 homodimer acts as a bridge to link two N termini of annexin proteins, inducing plasma membrane vesiculation in cells (5, 6). Interaction between S100A11 and DNA repair and recombination protein Rad54B participates in the repair of double-stranded DNA and regulation of the cell cycle (7). Furthermore, S100A11-RAGE interaction is correlated with the inflammation of chondrocytes (8). It has been reported that overexpression of S100A11 protein is associated with a number of cancers, including breast (9), colon (10), pancreatic (11), and papillary thyroid carcinoma (12). However, overexpression of S100A11 protein results in the contrary effect in ovarian (13) and bladder cancer (14). Reduced expression of S100A11 protein is correlated with progression of ovarian and bladder cancer, which has been investigated in previous studies. RAGE, the receptor of the immunoglobulin for signal transductions at the cel...

show abstract

Role of advanced glycation end products in cellular signaling

Cited by 957 publications

References 223 publications

Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium

Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium

Key structural and functional differences between early and advanced glycation products

Tranilast Blocks the Interaction between the Protein S100A11 and Receptor for Advanced Glycation End Products (RAGE) V Domain and Inhibits Cell Proliferation

Contact Info

Product

Resources

About