Blockade of receptor for advanced glycation endproducts: a new target for therapeutic intervention in diabetic complications and inflammatory disorders

Hudson, Barry I.; Bucciarelli, Loredana; Wendt, Thoralf; Sakaguchi, Taichi; Lalla, Evanthia; Qu, Wu; Lu, Yan; Lee, Larisse; Stern, David M.; Naka, Yoshifumi; Ramasamy, Ravichandran; Yan, Shi Du; Yan, Shi Fang; D’Agati, Vivette D.; Schmidt, Ann Marie

doi:10.1016/j.abb.2003.08.030

Cited by 154 publications

(127 citation statements)

References 66 publications

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“…Human diabetics, in whom insulin signaling is abnormal, accumulate high levels of advanced glycation end-products (Monnier & Cerami, 1982;Monnier et al, 1986;Hudson et al, 2003) and rats injected with streptozotocin to induce diabetes experimentally exhibit high levels of fluorescent age pigments in trigeminal neurons (Sugaya et al, 2004). Coupled with our observations in C. elegans, these data suggest that a conserved outcome of insulin signaling perturbation is age pigment accumulation.…”

Section: Insulin-like Signaling Has Major Impacts On Age Pigment Accusupporting

confidence: 59%

“…In higher organisms, advanced glycation end-products have been proposed to contribute to diabetic complications, including peripheral neuropathy, atherosclerosis, retinopathy, cataract formation and renal dysfunction (Monnier & Cerami, 1982;Monnier et al, 1986;Ulrich & Cerami, 2001;Hudson et al, 2003;Yamagishi et al, 2005), as well as to Alzheimer's disease pathology Yan et al, 1994;Sasaki et al, 1998). The dramatic increase in age pigment accumulation during the C. elegans post-reproductive phase and the striking relative elevation of age pigments in decrepit class C animals that have low life expectancy are consistent with the hypothesis that age pigments could actually promote the aging process.…”

Section: Do Age Pigments Promote Age-related Decline?mentioning

confidence: 99%

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In vivospectrofluorimetry reveals endogenous biomarkers that report healthspan and dietary restriction inCaenorhabditis elegans

et al. 2005

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SummaryAutofluorescent lipofuscin and advanced glycation end-products (age pigments) accumulate with age across phyla, yet little is understood about their formation under physiological conditions and their specific contributions to the aging process. We used in vivo spectrofluorimetry to quantitate autofluorescence in wild-type Caenorhabditis elegans and longevity mutants disrupted for distinct aspects of the aging process. In wild-type animals, age pigments increase into adulthood, accumulating slowly during the reproductive phase and more rapidly during the post-reproductive period. As in humans, insulin signaling influences age pigment accumulation -mutations that lower efficacy of insulin signaling and extend lifespan [ daf-2 ( e1370 ) insulin receptor and age-1 ( hx546 ) PI3-kinase] dramatically lower age pigment accumulation; conversely, elimination of the insulin-inhibited DAF-16/ FOXO transcription factor causes a huge increase in age pigment accumulation, supporting that the short-lived daf-16 null mutant is truly progeric. By contrast, mutations that increase mitochondrial reactive oxygen species production do not affect age pigment accumulation, challenging assumptions about the role of oxidative stress in generating these species in vivo . Dietary restriction reduces age pigment levels significantly and is associated with a unique spectral shift that might serve as a rapidly scored reporter of the dietary restricted state. Unexpectedly, genetically identical siblings that age poorly (as judged by decrepit locomotory capacity) have dramatically higher levels of age pigments than their same-aged siblings that appear to have aged more gracefully and move youthfully. Thus, high age pigment levels indicate a physiologically aged state rather than simply marking chronological time, and age pigments are valid reporters of nematode healthspan.

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Section: Insulin-like Signaling Has Major Impacts On Age Pigment Accusupporting

confidence: 59%

Section: Do Age Pigments Promote Age-related Decline?mentioning

confidence: 99%

In vivospectrofluorimetry reveals endogenous biomarkers that report healthspan and dietary restriction inCaenorhabditis elegans

et al. 2005

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“…Soluble RAGE functions as an anti‐inflammatory decoy receptor sequestering ligands of RAGE (eg, DAMP molecules such as S100A12) and thus abrogating cellular proinflammatory RAGE signaling,134 rendering sRAGE also a potential therapeutic target in patients with chronic inflammatory diseases 135. The lack of a correlation between serum sRAGE and S100A12 concentrations suggests that sRAGE is a nonspecific decoy receptor in dogs 27…”

Section: Biomarkers In Chronic Inflammatory Enteropathies Of Dogsmentioning

confidence: 99%

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

Heilmann

Steiner

2018

Veterinary Internal Medicne

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Chronic inflammatory enteropathies (CIE) in dogs are a group of disorders that are characterized by chronic persistent or recurrent signs of gastrointestinal disease and histologic evidence of mucosal inflammation. These CIEs are classified as either food‐responsive, antibiotic‐responsive, or immunosuppressant‐responsive enteropathy. Patients not clinically responding to immunomodulatory treatment are grouped as nonresponsive enteropathy and dogs with intestinal protein loss as protein‐losing enteropathy. Disease‐independent clinical scoring systems were established in dogs for assessment of clinical disease severity and patient monitoring during treatment. Histopathologic and routine clinicopathologic findings are usually not able to distinguish the subgroups of CIE. Treatment trials are often lengthy and further diagnostic tests are usually at least minimally invasive. Biomarkers that can aid in defining the presence of disease, site of origin, severity of the disease process, response to treatment, or a combination of these would be clinically useful in dogs with CIE. This article summarizes the following biomarkers that have been evaluated in dogs with CIE during the last decade, and critically evaluates their potential clinical utility in dogs with CIE: functional biomarkers (cobalamin, methylmalonic acid, folate, α1‐proteinase inhibitor, immunoglobulin A), biochemical biomarkers (C‐reactive protein, perinuclear anti‐neutrophilic cytoplasmic antibodies, 3‐bromotyrosine, N‐methylhistamine, calprotectin, S100A12, soluble receptor of advanced glycation end products, cytokines and chemokines, alkaline phosphatase), microbiomic biomarkers (microbiome changes, dysbiosis index), metabolomic biomarkers (serum metabolome), genetic biomarkers (genomic markers, gene expression changes), and cellular biomarkers (regulatory T cells). In addition, important performance criteria of diagnostic tests are briefly reviewed.

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“…Remarkably, treatment with exogenous sRAGE has been shown to suppress the acceleration of diabetic atherosclerosis in diabetic murine models (25). The association with specific disease conditions has prompted great interest in RAGE as a therapeutic target (26)(27)(28).…”

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confidence: 99%

The Extracellular Region of the Receptor for Advanced Glycation End Products Is Composed of Two Independent Structural Units

et al. 2007

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The receptor for advanced glycation end products (RAGE) is an important cell surface receptor being pursued as a therapeutic target because it has been implicated in complications arising from diabetes and chronic inflammatory conditions. RAGE is a single membrane spanning receptor containing a very small ~40 residue cytosolic domain and a large extracellular region comprised of 3 Ig-like domains. In this study, high level bacterial expression systems and purification protocols were generated for the extracellular region of RAGE (sRAGE) and the five permutations of single and tandem domain constructs to enable biophysical and structural characterization of its tertiary and quaternary structure. The structure and stability of each of these six protein constructs was assayed by biochemical methods including limited proteolysis, dynamic light scattering, CD, and NMR. A homology model of sRAGE was constructed to aid in the interpretation of the experimental data. Our results show that the V and C1 domains are not independent domains, but rather form an integrated structural unit. In contrast, C2 is attached to VC1 by a flexible linker and is fully independent. The interaction with a known RAGE ligand, Ca 2+ -S100B, was mapped to VC1, with the major contribution from the V domain but clearly defined secondary effects from the C1 domain. The implications of these results are discussed with respect to models for RAGE signaling.

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Blockade of receptor for advanced glycation endproducts: a new target for therapeutic intervention in diabetic complications and inflammatory disorders

Cited by 154 publications

References 66 publications

In vivospectrofluorimetry reveals endogenous biomarkers that report healthspan and dietary restriction inCaenorhabditis elegans

In vivospectrofluorimetry reveals endogenous biomarkers that report healthspan and dietary restriction inCaenorhabditis elegans

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

The Extracellular Region of the Receptor for Advanced Glycation End Products Is Composed of Two Independent Structural Units

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